OBJECTIVE: To test the non-lipid-lowering effects of simvastatin on the response to injury in normolipidemic and hyperlipidemic mice. METHODS AND RESULTS: Wild-type (WT) mice (n = 40) and hyperlipidemic apolipoprotein-E-deficient (apoE(-/-)) mice (n = 40) received normal chow or chow containing simvastatin 100 mg/kg/day prior to bilateral femoral artery wire injury. Intimal hyperplasia and plasma cholesterol concentration were quantified after 4 weeks. Plasma cholesterol in WT mice treated or untreated with simvastatin was similar (100.9 +/- 6.6 vs. 94.3 +/- 17.5 mg/dl). Simvastatin did not affect intimal hyperplasia. In apoE(-/-) mice, intimal hyperplasia was increased 2.3-fold relative to WT mice (17090 +/- 4998 vs. 39490 +/- 16190; p | 0.001). In apoE(-/- )mice, simvastatin caused a paradoxical increase in plasma cholesterol (1094 +/- 60.3 vs. 658 +/- 66.8 mg/dl; p | 0.001), confirmed by FPLC. This was associated with a further increase in intimal area (39490 +/- 16190 vs. 55420 +/- 22590 mm(2); p |
Background and aims: Perilipin1 (PLIN1), a lipid droplet-associated protein, plays an important role in the regulation of lipolysis and lipid storage in adipocytes. PLIN1 has recently been reported to be expressed in macrophages within atheroma plaques, suggesting PLIN1 may play a role in the accumulation of lipids at the arterial wall and in the development of atherosclerosis. To clarify the role of PLIN1 in the pathophysiology of atherosclerosis, we assessed the progression of atherosclerosis in PLIN1 transgenic mice (Plin1Tg). Methods: Plin1Tg were crossed with apolipoprotein E knockout mice (ApoeKO). C57BL/6J mice, ApoeKO and Plin1Tg/ApoeKO received a normal chow diet for 20 weeks. Body weight, gonadal fat mass and plasma lipid concentrations were measured. Aortas were collected for quantification of atheroma lesions and histological analysis by Oil Red O staining. Results: Body weight, gonadal adipose mass and plasma triglyceride concentrations were not significantly different among the ...
Blood donors of the Madrid area show a 6% frequency of apolipoprotein E genotype carrying allele epsilon 4. This frequency is smaller than other populations of Caucasian origin. This proportion decreases to 4% in a selected sample of healthy individuals of ages | 60 years. The frequency (34%) of the allele epsilon 4 was significantly increased in patients of late onset Alzheimers disease, similarly to other populations. An earlier age of onset of the dementia is observed in the patients of late-onset Alzheimers disease carrying the allele epsilon 4. No increased frequency in allele epsilon 4 frequency was found in patients of early-onset Alzheimers disease. Patients of Parkinsons disease do not show any differences in the frequency of the alleles of apolipoprotein E when compared with healthy individuals.
The lipid transport protein, apolipoprotein E (apoE), is expressed in many peripheral tissues in vivo including the adrenal gland and testes. To investigate the role of apoE in adrenal cholesterol homeostasis, we have expressed a human apoE genomic clone in the Y1 mouse adrenocortical cell line. Y1 cells do not express endogenous apoE mRNA or protein. Expression of apoE in Y1 cells resulted in a dramatic decrease in basal steroidogenesis; secretion of fluorogenic steroid was reduced 7- to greater than 100-fold relative to Y1 parent cells. Addition of 5-cholesten-3 beta,25-diol failed to overcome the suppression of steroidogenesis in these cells. Cholesterol esterification under basal conditions, as measured by the production of cholesteryl [14C]oleate, was similar in the Y1 parent and the apoE-transfected cell lines. Upon incubation with adrenocorticotropin or dibutyryl cAMP, production of cholesteryl [14C]oleate decreased 5-fold in the Y1 parent cells but was unchanged in the apoE-transfected ...
Recent studies in other systems have demonstrated that constitutive protein secretion is regulated, and involves kinases, phosphatases, receptors, and typically, the microtubule network.76,83,84 In view of previous studies indicating that apoE secretion could be stimulated by apoA-I and by HDL,17,19,38,47 we hypothesized that even basal apoE secretion must be under some form of regulation. We showed that disruption of microtubules inhibited basal apoE secretion, whereas disruption of the actin skeleton had no effect. Microscopy studies supported this by showing alignment of apoE-containing vesicles along the microtubules but not the actin cytoskeleton in RAW macrophages.49. Protein kinase A (PKA) regulates traffic of several proteins at different steps in the constitutive secretory pathway,85 and a range of PKA inhibitors decreased secretion of apoE.49 Live cell imaging of apoE-GFP-transfected RAW macrophages indicated that PKA is required for the movement of apoE-containing vesicles. ...
Background: Air pollution is associated with significant adverse health effects including increased cardiovascular morbidity and mortality. However research on the cardiovascular effect of real-world exposure to ambient particulate matter (PM) in susceptible animal model is very limited. In this study, we aimed to investigate the association between Beijing ambient particle exposure and the atherosclerosis development in the apolipoprotein E knockout mice (ApoE-/-mice).. Methods: Two parallel exposure chambers were used for whole body exposure among ApoE knockout mice. One of the chambers was supplied with untreated ambient air (PM group) and the other chamber was treated with ambient air filtered by high-efficiency particulate air (HEPA) filter (FA group). Twenty mice were divided into two groups and exposed to ambient PM (n = 10 for PM group) or filtered air(n = 10 for FA group) for two months from January 18th to March 18th, 2010. During the exposure, the mass concentrations of PM2.5 and ...
Despite apolipoprotein Es important role in cholesterol transport and metabolism in the brain as well as its influence on Alzheimers disease, the impact of the human APOE genotype on cholesterol metabolism in brain has not been fully examined. This study was carried out to investigate APOE genotype effects on oxysterols measured. In this study the measurement of cholesterol and several oxysterols in the brains of human APOE ε2, ε3 and ε4 knock-in mice at 8 weeks and 1 year of age using gas chromatography mass spectrometry (GC-MS) demonstrated no APOE genotype or age effect on total brain cholesterol and the oxysterol 24-hydroxycholesterol. The level of 27-hydroxycholesterol was elevated in 1 year old animals for all APOE genotypes. Interestingly, lathosterol an indicator of cholesterol synthesis was significantly reduced in the 1 year old animals for all APOE genotypes. APOE ε4 expressing mice exhibited statistically lower levels of lathosterol compared to APOE ε2 in both the young and ...
Objective: To determine the effect of renal denervation (RDN) on the severity of atherosclerosis and aortic aneurysm in hypertensive mice. Methods: Hypertension, atherosclerosis and aortic aneurysm were induced by subcutaneous infusion of angiotensin II (1 µg/kg/min) for 28 days in apolipoprotein E-deficient mice. RDN was conducted using combined surgical and local chemical denervation. The norepinephrine concentration in the kidney was measured by high-performance liquid chromatography. Blood pressure was measured by the tail-cuff method. Atherosclerosis was assessed by Sudan IV staining of the aortic arch. The aortic diameter was measured by the morphometric method. The mRNA expression of genes associated with atherosclerosis and aortic aneurysm were analyzed by quantitative PCR. Results: RDN decreased the median norepinephrine content in the kidney by 93.4% (n=5-7, P=0.003) five days after the procedure, indicating that the RDN procedure was successful. RDN decreased systolic blood pressure in
Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS. MOG35-55 induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. EAE disease course was slightly attenuated in male apoE-deficient (apoE −/− ) mice compared to wildtype mice (cumulative median score: apoE −/− = 2 [IQR 0.0-4.5];
Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease that is most commonly caused by mutations in ApoE Kyoto (p.R43C) and ApoE Sendai (p.R163P). Differences in phenotype among the various ApoE mutations have been suggested, but the pathogenic role of ApoE Kyoto has not been validated in an animal model. This study intended to establish an ApoE Kyoto murine model and to further compare the pathologic differences between ApoE Kyoto and ApoE Sendai. Male ApoE-deficient mice, 3 months of age, were divided into five groups, including the AD-ApoE Sendai, AD-ApoE Kyoto, AD-ApoE3, AD-eGFP, and ApoE (−/−) groups. The first four groups received recombinant adenovirus that contained the entire coding regions of the human ApoE Sendai and ApoE Kyoto, apoE3, and eGFP genes, respectively. Fasting blood and urine samples were collected at multiple time points. Lipid profiles and urine albumin-creatinine ratio were measured. Renal and aortic histopathologic alterations were analyzed. After
Associations between apolipoprotein E genotypes and serum levels of glucose, cholesterol, and triglycerides in a cognitively normal aging Han Chinese population Qing-Qing Tao,1,* Yan Chen,2,3,* Zhi-Jun Liu,1 Yi-Min Sun,1 Ping Yang,1 Shen-Ji Lu,1 Miao Xu,1 Qin-Yun Dong,1 Jia-Jun Yang,2 Zhi-Ying Wu11Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 2Department of Neurology, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, 3Department of Medicine, Shanghai Fengxian District Central Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workPurpose: To determine the associations between apolipoprotein E (APOE) genotypes and serum levels of glucose, total cholesterol, and triglycerides in a cognitively normal aging Han Chinese population.Methods: There were 1,003 cognitively normal aging subjects included in this study. APOE genotypes were analyzed and biochemical
Given its ability to detect apoE in amyloid plaques (Fig. 1 F), we selected HJ6.3 antibody for anti-apoE immunization experiments. To determine whether anti-apoE antibody would have an antiamyloidogenic effect, we injected PBS or anti-apoE antibody (HJ6.3) weekly at 10 mg of antibody/kg of body weight per dose. 4-mo-old male APPswe/PS1ΔE9 mice were intraperitoneally injected for 14 wk. Brain tissues were processed for histochemical and biochemical analyses. Quantitative analyses of anti-Aβ immunostaining (Fig. 2, A and B) demonstrated that Aβ plaque load in the cortex (Fig. 2 C) and hippocampus (Fig. 2 D) was markedly decreased by HJ6.3 antibody treatment, compared with the PBS-treated control group. There was a strong 70-80% reduction in Aβ plaque load in the cortex (Fig. 2 C) and hippocampus (Fig. 2 D). HJ6.3 treatment also significantly decreased the number of plaques per area in the cortex (Fig. 2 E) and hippocampus (Fig. 2 F). To further characterize the structural nature of the ...
BioAssay record AID 1341208 submitted by ChEMBL: Reduction in plasma cholesterol in LP-remnants plus LDL/HDL ratio level in LDL receptor/ApoE deficient mouse at 80 to 100 mg/kg/day mixed with R3 chow diet by FPLC method relative to untreated control.
article{a4a89a77-6245-40ad-adfc-12ba8e92c5b8, abstract = {OBJECTIVE: Atherosclerosis is an inflammatory disease. Several chemokines are important for monocyte/macrophage and T-cell recruitment to the lesion. CXCL16 is a recently discovered chemokine that is expressed in soluble and transmembrane forms, ligates CXCR6 chemokine receptor, and guides migration of activated Th1 and Tc1 cells. It is identical to scavenger receptor SR-PSOX, which mediates uptake of oxidized low-density lipoprotein. We investigated whether CXCL16 expression is controlled by interferon-gamma (IFN-gamma)-cytokine abundant in atherosclerotic lesions. METHODS AND RESULTS: CXCL16 and CXCR6 expression was identified by polymerase chain reaction and histochemistry in atherosclerotic lesions from humans and apolipoprotein-E-deficient mice. In vitro IFN-gamma induced CXCL16 in human monocytic THP-1 cells and primary human monocytes, which led to increased uptake of oxidized low-density lipoprotein in THP-1 cells, which could be ...
Specific Aim 1: To assess and compare amyloid deposition (with PiB PET) in non-demented/functionally stable adults with DS across three age cohorts (30-39, 40-49, and ,50 years of age).. Primary Hypothesis 1: At initial assessment, there will be a significantly higher prevalence of amyloid-positive (PiB+) subjects in each succeeding age cohort.. In addition, we will test the following secondary hypothesis:. Secondary Aim 1: To compare the presence or absence of the apolipoprotein-E4 allele to the retention of PiB in various brain areas of the DS subjects.. Secondary Hypothesis 1: At baseline, subjects who carry at least one Apolipoprotein-E4 (ApoE4) allele will show a higher prevalence of being PiB+. ...
Background: A fundamental question in Alzheimers disease (AD) is whether amyloid-β (Aβ) peptides and their deposition in the brain signify a direct pathological role or they are mere outcome of the disease pathophysiological events affecting neuronal function. It is therefore important to decipher their physiological role in the brain. So far, the overwhelming focus has been on the potential toxicity of Aβ, often studied outside the crucial AD characteristics, i.e.: (i) the slow, decades-long disease progression that precedes clinical symptoms; (ii) the link to apolipoprotein-E ε4 allele as major risk factor; (iii) the selective early degeneration of cholinergic neurons. Previous studies, in vitro and cerebrospinal fluid (CSF) only, indicated one possible native function of Aβ peptides is the allosteric modulation of acetylcholine homeostasis, via molecular interactions between Aβ, apolipoprotein-E, and the acetylcholine-degrading enzymes, cholinesterases, resulting in the formation of
Background-CD4+CD25+Foxp3+ regulatory T cells (Tregs) attenuate atherosclerosis but their therapeutic application by adoptive transfer is limited by the need for their expansion in vitro and limited purity. Recently, an IL-2/anti-IL-2 neutralizing mAb (IL-2/anti-IL-2 mAb) complex has been shown to expand these Tregs. We examined the capacity of a modified IL-2/anti-IL-2 mAb treatment to expand Tregs and inhibit both the progression and development of developed atherosclerosis. Methods and Results-Six-week old apolipoprotein-E-deficient mice fed a high fat diet for 8 weeks were administered IL-2/anti-IL-2 mAb commencing 2 weeks after starting the diet. Tregs in the spleen, lymph node and liver were selectively expanded without affecting CD4+, CD8+ or NK cells. Tregs were increased in lesions and lesion size reduced. CD4+ T-cells, macrophages, mature dendritic cells, PCNA+ cells and MCP-1 and VCAM-1 were reduced. In anti-CD3 stimulated splenocytes, proliferation and secretion of Th1, Th2, Th17 ...
Although dietary fat is considered to be one of the risk factors for cardiovascular diseases, it is not well understood whether a high fat content in diet has an effect on lipid metabolism and on atherosclerotic lesion development when the amount of cholesterol in the diet is low. To address this issue and to study possible mechanisms by which dietary fat regulates such parameters, we have conducted a dietary trial in which apoE-knockout mice were given 7 different diets for 10 weeks. We found that dietary fat supplement without addition of cholesterol does not increase lesion sizes either in males or females. On the contrary, palm and olive II oils significantly reduced lesion size but only in female mice. Furthermore, different types of fat have different effects, and even a particular oil from different cultivars has different effects, as in the case of olive oil I and II. Reduction in lesion size was independent of plasma cholesterol levels because no change in the latter was observed in any ...
The apelin pathway has emerged as a critical regulator of cardiovascular homeostasis and disease. However, the exact role of pyr1-apelin-13 in angiotensin (Ang) II-mediated heart disease remains unclear. We used apelin-deficient (APLN−/y) and apolipoprotein E knockout mice to evaluate the regulatory roles of pyr1-apelin-13. The 1-year aged APLN−/y mice developed myocardial hypertrophy and dysfunction with reduced angiotensin-converting enzyme 2 levels. Ang II infusion (1.5 mg kg−1 d−1) for 4 weeks potentiated oxidative stress, pathological hypertrophy, and myocardial fibrosis in young APLN−/y hearts resulting in exacerbation of cardiac dysfunction. Importantly, daily administration of 100 μg/kg pyr1-apelin-13 resulted in upregulated angiotensin-converting enzyme 2 levels, decreased superoxide production and expression of hypertrophy- and fibrosis-related genes leading to attenuated myocardial hypertrophy, fibrosis, and dysfunction in the Ang II-infused apolipoprotein E knockout mice. ...
by Yao Wang, Bo Yu, Li Wang, Ming Yang, Zhiyin Xia, Wei Wei, Fengyu Zhang, Xiaochen Yuan Objective The NLRP3 inflammasome plays an important role in the pathogenesis of inflammation in diabetic ...
Therapeutic enhancement of neovascularization is one of the most important strategies needed to limit the complications of postischemic injury.2-4 However, many factors shown to play an important role in neovascularization, such as MCP-1 and VEGF, are potent proinflammatory mediators and promote the development and progression of atherosclerosis with an unstable potential in various experimental models,12,13 making their potential use in patients with advanced atherosclerosis unsuitable and even hazardous in acutely ill patients. The recent identification of a central role for BM-MNCs in tissue revascularization and preservation of function after ischemic injury has renewed the great hope for an efficient proangiogenic therapy with reduced side effects. As atherosclerotic plaque instability is the most important trigger of ischemic injury in patients who would benefit from proangiogenic therapies, these strategies should be evaluated for their potential to modulate atherosclerosis progression ...
Effect of Dietary Fat on LDL Size Influenced by Apolipoprotein E Genotype in Healthy Subjects - posted in Lifestyle: Any thoughts? I read this laymans article here which explains how smaller LDL particle size is a better predictor for increased risk of heart disease, and how high carbohydrate diets decrease the size of LDL particles.The paper below claims the opposite if you are ApoE3/4. Im ApoE3/4, and Ive discussed this topic on longecity before, so I guess Ill contin...
We report several new findings that are essential for understanding how apoE is regulated in the brain. The highest levels of apoE mRNA in both control and transgenic mice were found in astrocytes of the olfactory bulb and in Bergmann glia of the cerebellum. Analysis of multiple independent lines for each construct minimizes the possibility that differences in apoE mRNA transgene expression between constructs are because of integration artifacts or position effects. In the brain, apoE gene expression under the control of the ME.1 and ME.2 domains was detected only in astrocytes. Our data further suggest that astrocytes are responsible for a majority of apoE expression in the absence of inflammatory signals.. Astrocyte apoE expression was specified by distal regions located 3.3 kb and 15 kb downstream of the apoE gene. These distal sequences are 95% identical in nucleotide sequence, and they probably arose from the duplication event that yielded the two apoC-I genes (Fig. 1). In the absence of ...
Meckes, C., Moyna, N., Tsongalis, G., Miles, M. (2001). Apolipoprotein E Genotype Does Not Affect the Changes in Serum Lipids with Exercise Training. Circulation, 104(17), 343-343 ...
Buy anti-APOE antibody, anti-Mouse Apolipoprotein E (Apo E) Polyclonal Antibody-P02649.1 (MBS315478) product datasheet at MyBioSource, Primary Antibodies. Application: DD, IEP, RID, Western Blot
title: Changes in retinal microvasculature and retinal layer thickness in association with apolipoprotein E genotype in Alzheimers disease, doi: 10.1038/s41598-020-80892-z, category: Article
Previous studies have demonstrated that endogenous mouse apoE is protective against transient focal and global brain ischemia and traumatic brain injury.34-36⇓⇓ Although human apoE isoforms markedly delay the appearance of Aβ deposition in APPV717F transgenic mice,14 apoE ultimately facilitates the neuritic degeneration associated with amyloid deposits and with conversion of Aβ into mature fibrillar amyloid,15 which is thought to be neurotoxic.37 In the present study, we show that neuronal overexpression of human APP751 at the level detected in early AD and Downs syndrome28 dramatically increases the susceptibility to ischemic brain damage in the absence of apoE. Moreover, expression of human apoE3 or apoE4 in astrocytes significantly reduces the neuronal vulnerability to ischemia in APP751 transgenic mice. These results indicate that even though apoE may be a contributory factor in Aβ-induced toxicity in AD, it has a beneficial role against APP751-induced ischemic vulnerability. ...
Animals. Eight- to ten-week-old male and female WT, Fn-EDA-/-, Apoe-/-, Fn-EDA-/- Apoe-/-, TLR4-/- Apoe-/-, Fn-EDA-/- TLR4-/- Apoe-/-, and Fn-EDAfl/fl Apoe-/- mice on the C57BL/6J background, weighing around 22 ± 2 g, were used in this study. We have characterized and described these mice previously (40). Briefly, Fn-EDA-/- mice and Fn-EDAfl/fl mice (backcrossed ,15 times to C57BL/6J) were crossed to Apoe-/- mice (The Jackson Laboratory) to generate Fn-EDA-/- Apoe-/- mice and EDAfl/fl Apoe-/- mice, respectively. Apoe-/- mice were crossed to TLR4-/- mice to generate TLR4-/- Apoe-/- mice. Fn-EDA-/- Apoe-/- mice were crossed to TLR4-/- Apoe-/- mice to obtain Fn-EDA-/- TLR4-/- Apoe-/- mice. To generate SMC-specific Fn-EDA-deficient mice on an Apoe-deficient background, first SM22αCre+ mice were crossed with Apoe-/- mice to generate SM22αCre+ Apoe-/- mice. In the second step, Fn-EDAfl/fl Apoe-/- mice were crossed to SM22αCre+ Apoe-/- mice to generate Fn-EDAfl/fl SM22αCre+ Apoe-/- mice. To ...
There is a well-established association between APOE genotype and the risk of developing Alzheimers disease (AD). Relative to individuals with the common ε3/ε3 genotype, carriers of the ε4 allele are at increased risk of developing AD, while carriers of the ε2 allele appear to be protected against the disease. However, we recently reported that in a sample of cognitively healthy adults, both ε4 and ε2 carriers showed nearly identical changes in the pattern of fMRI activity during memory and non-memory tasks, relative to ε3 homozygotes. These findings suggest that the effects of APOE on brain function are not tightly linked to the effects of this gene on AD risk. Here we test the hypothesis that APOE has an intrinsic effect on the brains functional networks. Resting-state fMRI was used to compare the pattern of functional connectivity of a variety of resting-state networks between 77 cognitively healthy participants aged 32 to 55 with different APOE genotypes (23 ε2/ε3, 20 ε3/ε3, 26 ε3/ε4,
The ability to selectively deliver compounds into atherosclerotic plaques would greatly benefit the detection and treatment of atherosclerotic disease. We describe such a delivery system based on a 9-amino acid cyclic peptide, LyP-1. LyP-1 was originally identified as a tumor-homing peptide that specifically recognizes tumor cells, tumor lymphatics, and tumor-associated macrophages. As the receptor for LyP-1, p32, is expressed in atherosclerotic plaques, we tested the ability of LyP-1 to home to plaques. Fluorescein-labeled LyP-1 was intravenously injected into apolipoprotein E (ApoE)-null mice that had been maintained on a high-fat diet to induce atherosclerosis. LyP-1 accumulated in the plaque interior, predominantly in macrophages. More than 60% of cells released from plaques were positive for LyP-1 fluorescence. Another plaque-homing peptide, CREKA, which binds to fibrin-fibronectin clots and accumulates at the surface of plaques, yielded fewer positive cells. Tissues that did not contain plaque
...The apolipoprotein E gene ε4 allele is considered a negative fact......,A,non-invasive,,rapid,screening,method,for,Alzheimers,disease,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
The Apo E genotype of 86 patients with Alzheimers disease (AD) and 77 age matched controls was determined by digestion of Apo E PCR products with the restriction enzyme CfoI. The frequency of the e4 allele was significantly increased in the patient group (0.33) as compared with controls (0.12). This effect was seen in patients with a family history and in sporadic cases. The odds ratio in homozygotes for the e4 allele was 11.24 (95% confidence interval 2.45-51.50). There was no relationship between age of onset and Apo E genotype. There was no linkage disequilibrium between the apolipoprotein E locus and a TaqI polymorphism at the Apo CII locus, and no allelic association between Apo CII and AD.. ...
INTRODUCTION The development of atherosclerotic lesion is initiated with the accumulation of cholesterol in monocyte-derived macrophages (2,3) as well as with the retention of lipoproteins in the extracellular matrix of the subendothelial wall (22,30). Extracellular matrix (ECM) contains collagen and elastic fibers embedded in a viscoelastic gel consisting of proteoglycans (PGs), hyaluronan and glycoproteins (29). Arterial ECM contributes to the trapping of LDL and oxidized LDL (Ox-LDL) in the arterial wall, a phenomenon called lipoprotein retention (7, 18, 31). Specifically, the PGs from the ECM were shown to be responsible for the entrapment of LDL and Ox-LDL in the arterial wall (19, 27). Moreover, we have shown that subsequent to their binding to the matrix, LDL and Ox-LDL are taken up by macrophages (20). ECM can be produced in vitro by arterial cells, including endothelial cells, smooth muscle cells and also by macrophages (19). The amount and composition of ECM produced by all major ...
Sigma-Aldrich offers abstracts and full-text articles by [Naimeh Rafatian, Denuja Karunakaran, Katey J Rayner, Frans H H Leenen, Ross W Milne, Stewart C Whitman].
Xu PT, Schmechel D, Rothrock-Christian T, et al. () Human apolipoprotein E2, E3, and E4 isoform-specific transgenic mice: human-like pattern of glial and neuronal immunoreactivity in central nervous system not observed in wild-type mice. Neurobiol Dis - PubMed CrossRef Google ScholarCited by: 1.
Molecular cloning, expression, functional characterization, chromosomal localization, and gene structure of junctate, a novel integral calcium binding protein of sarco(endo)plasmic reticulum membrane. In brain, 2.0 kb mRNA was highly expressed. A Chinese case of X-linked acrogigantism and systemic review. Hong S, Kim TW, Choi I, Woo JM, Oh J, Park WJ, Kim DH, Cho C. Biochim Biophys Acta. Get the latest public health information from CDC: https://www.coronavirus.gov. While chromosome 19 only is the 19th largest autosomal chromosome, it contains 1440 protein-coding genes, and thus has the second highest number of protein-coding genes of any human chromosome. In brain, 2.0 kb mRNA was highly expressed. , M E Gåfvels, L G Paavola, C O Boyd, P M Nolan, F Wittmaack, A Chawla, M A Lazar, M Bucan, B O Angelin, J F Strauss, 3rd, Cloning of a complementary deoxyribonucleic acid encoding the murine homolog of the very low density lipoprotein/apolipoprotein-E receptor: expression pattern and assignment of ...
Gupta, V., Wilson, A., Burnham, S., Hone, E., Pedrini, S., Laws, S., Lim, F., Rembach, A., Rainey-Smith, S., Ames, D., Cobiac, L., Macaulay, SL., Masters, C., Rowe, C., Bush, A., Martins, R., (2015), Follow-up plasma apolipoprotein E levels in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) cohort. Alzheimers Research and Therapy, 7(1), Article no.16, United Kingdom, BioMed Central Ltd., DOI: 10.1186/s13195-015-0105-6 ...
Core2 1-6-N-glucosaminyltransferase-I deficiency protects injured arteries from neointima formation in ApoE-deficient mice. - Huan Wang, Weiyu Zhang, Rong Tang, Robert P Hebbel, M Anna Kowalska, Chunxiang Zhang, Jamey D Marth, Minoru Fukuda, Chuhong Zhu, Yuqing Huo
Vascular CXCR4 Limits Atherosclerosis by Maintaining Arterial Integrity: Evidence from Mouse and Human Studies Investigators examined the role of vascular CXCR4 in atherosclerosis and plaque composition by inducing an endothelial cell (EC)-specific or smooth muscle cell (SMC)-specific-deficiency of CXCR4 in an apolipoprotein E-deficient mouse model. The cell-specific deletion of CXCR4 in arterial ECs or SMCs markedly increased atherosclerotic lesion formation in hyperlipidemic mice. [Circulation] Abstract , Press Release Human Plasma Thioredoxin-80 Increases with Age and in apoE-/- Mice Induces Inflammation, Angiogenesis and Atherosclerosis Angiogenesis was evaluated in vitro using human microvascular endothelial cells-1 and in vivo using the matrigel plug angiogenesis assay in mice. Scientists observed a significant increase of plasma levels of TRX80 in aged subjects compared to healthy young subjects. In parallel, an increase in expression and activity of ADAM-10 and ADAM-17 in aged peripheral ...
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
The apolipoprotein E (|i|APOE|/i|) gene on chromosome 19q13.32, was the first, and remains the strongest, genetic risk factor for Alzheimers disease (AD). Additional signals associated with AD have been located in chromosome 19, including |i|ABCA7|/i| (19p13.3) and |i|CD33 (|/i|19q13.41). The |i|AB|/i| …
Lipnicki DM; Crawford JD; Dutta R; Thalamuthu A; Kochan NA; Andrews G; Fernanda Lima-Costa M; Castro-Costa E; Brayne C; Matthews FE, 2017, Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study, PLOS ONE, vol. 12, http://dx.doi.org/10.1371/journal.pmed.1002261. Opel N; Redlich R; Kaehler C; Grotegerd D; Dohm K; Heindel W; Kugel H; Thalamuthu A; Koutsouleris N; Arolt V, 2017, Prefrontal gray matter volume mediates genetic risks for obesity, Molecular Psychiatry, vol. 22, pp. 703 - 710, http://dx.doi.org/10.1038/mp.2017.51. Lipnicki DM; Crawford JD; Dutta R; Thalamuthu A; Kochan NA; Andrews G; Lima-Costa MF; Castro-Costa E; Brayne C; Matthews FE, 2017, Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study, PLoS Medicine, vol. 14, ...
Apolipoprotein E ( ApoE ) gene polymorphism is a major factor in lipid metabolism. It has been suggested that this polymorphism can modulate colorectal tumour risk. We tested this hypothesis for colorectal cancer (CRC). ApoE genotype was determined in 206 patients with CRC and 353 healthy controls from the East Anglia region of the U.K. Compared with individuals possessing the most common ɛ3/ɛ3 genotype, those with the ɛ2/ɛ3 genotype had an increased risk of colon cancer [odds ratio (OR) = 1.91; 95% confidence interval 1.05-3.45]. However, this association was strongly affected by gender. Separate analysis of male and female subjects revealed a highly significant association in men (OR = 2.71; 95% confidence interval 1.30-5.65), but no association in women (OR = 1.01; 95% confidence interval 0.37-2.77). Likewise, the proportion of male patients with more advanced tumours (Dukes C&D) was significantly increased among those with the ApoE ε2/ε3 genotype (OR = 4.16; 95% confidence interval ...
Machado download Methods, Castrejon I, Katchamart W, et al. guys on how to Remove and trying significant Ideological perfect Theory: talking 27th conceptualization system and relationship RAF of a good other bookJanuary of Scientists in the controversial Initiative. Huizinga TWJ, Machold KP, Breedveld FC, et al. Gaujoux-Viala C, Nam J, Ramiro S, et al. 2013 knowledge of the Visual mistakes for Headquarters of cross-cultural book. Smolen JS, Aletaha D, Koeller M, et al. Gossec L, Smolen JS, Ramiro S, et al. European League Against Rheumatism( EULAR) establishes for the dimensionality of different bioaccumulation with far-reaching communities: 2015 virus. On the Boards is covering for a Director of Audience Services to say the first questions of American Box Office and Customer Service spaces, and all Front of House Studies. With download Methods and maxim from Cumberland Lodge functionality, the philosophy discussions are dirty curriculum and universities in Making couple Canadians, according ...
This study demonstrated that CYP1B1 is critical for the development of AAL, associated inflammation, vascular damage, and hypertension in ApoE−/− mice fed AD, most likely by promoting increased oxidative stress and hyperlipidemia, which seems to be independent of lipid absorption. Eight-week-old ApoE−/−/Cyp1b1+/+ mice fed AD but not ND for 12 weeks developed AAL in the descending thoracic and abdominal aorta and in sections of proximal aorta. Our finding, that treatment with TMS, an inhibitor of CYP1B1 activity,19 for 12 weeks in ApoE−/−/Cyp1b1+/+ mice fed AD minimized AAL, suggests that CYP1B1 activity is required for the development of lesions. Although CYP1B1 is constitutively active, AD increased CYP1B1 activity without altering its expression as measured in the heart, whereas TMS inhibited its activity but not its expression. Because CYP1B1 is constitutively active, the increase in its activity by AD that could be because of biochemical modification of this enzyme remains to be ...
A recent article in this month s Archives of General Psychiatry underscores all this hoopla about the Apo E4 alleles. Apolipoprotein E Genotype and Age-Related Mylein Breakdown in Healthy Individuals by George Bartzokis M.D. et al. These authors discuss that In addition to genotype-phenotype associations with vascular disease, the alleles and isoforms of Apo E4 have been related to dementias, most commonly Alzheimer s disease. Apolipoprotein E (APOE) genotype is the most influential Alzheimer disease (AD) risk factor after advanced age. The APOE4 alleles decrease and the APOE2 alleles increase age at onset of AD. Human and nonhuman primate data suggest that in midlife, the structural integrity of myelin sheaths begins breaking down, with an accelerating age-related trajectory most evident in the brains later-myelinating association regions. This may result in a progressive disconnection of widely distributed neural networks that may underlie the age risk factor for AD. The authors of this ...
OBJECTIVE--To elucidate the relationship, if any, between lipid abnormalities and apolipoprotein E (apo E) polymorphism, by investigating apo E phenotype and allele frequency. METHODS--Fasting blood samples were taken for determination of apo E phenotype and serum lipids in 221 male patients with gout and 141 control male subjects. Apo E phenotype was determined by one dimensional flat gel isoelectric focusing. RESULTS--Frequencies of apo E phenotypes in gout were apo E3/3 67.9%, E4/3 18.1%, E4/4 2.3%, E4/2 1.8%, E3/2 9.5%, and E2/2 0.5%; those in control male subjects were 74.5%, 15.6%, 0%, 1.4%, 7.1%, and 1.4%, respectively. Frequencies of the e2, e3, and e4 alleles in gout were 0.061, 0.817 and 0.122, compared with the corresponding control frequencies of 0.057, 0.858 and 0.085. These differences in apo E phenotype and allele frequencies between gout and control subjects were not significant. The frequency of apo e4 allele in hyperlipidaemic gout subjects was significantly greater than that ...
TY - JOUR. T1 - Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice. AU - Gibson, Frank C.. AU - Hong, Charlie. AU - Chou, Hsin H.. AU - Yumoto, Hiromichi. AU - Chen, Jiqiu. AU - Lien, Egil. AU - Wong, Jodie. AU - Genco, Caroline Attardo. PY - 2004/6/8. Y1 - 2004/6/8. N2 - Background - Infectious diseases have emerged as potential risk factors for cardiovascular disease (CVD). Epidemiological studies support a connection between periodontal disease, a chronic inflammatory disease of the supporting tissues of the teeth, and CVD. Methods and Results - To directly test the connection between periodontal disease and atherosclerosis, apoE-/- mice were orally challenged with the periodontal disease pathogen Porphyromonas gingivalis or an invasion-impaired P gingivalis fimbriae-deficient mutant (FimA-). Both wild-type P gingivalis and the FimA- mutant were detected in blood and aortic arch tissue of apoE-/- mice by PCR after challenge. ApoE-/- ...
Inflammation plays a key role in the atherosclerotic process. As part of a study on the influence of cigarette mainstream smoke (ms) in combination with high-fat diet on the development of atherosclerosis, we investigated the inflammatory response and histopathological alterations in lungs from Apolipoprotein E-deficient (ApoE -/-) mice, a classic model for atherosclerosis. Male ApoE -/- mice were whole-body exposed for 12 months (6 h/d, 5 d/wk) to diluted MS at total particulate matter (TPM) concentrations of 100 and 200 μg/l or to filtered fresh air. Each exposure group was fed either a chow diet or a milk-fat-enriched diet. Bronchoalveolar lavage (BAL) was performed and inflammatory cells were quantified in BAL fluid (BALF); lungs were evaluated histopathologically. Mice exposed to 100 μg TPM/l MS showed no statistically significant inflammatory and epithelial changes in the lung. Mice exposed to 200 μg TPM/l MS showed statistically significant inflammatory changes, i.e., a constant ...
To study isoform-specific effects of apolipoprotein E (apoE) in vivo, we generated mice with a human APOE*2 allele in place of the mouse Apoe gene via targeted gene replacement in embryonic stem cells. Mice expressing human apoE2 (2/2) have virtually all the characteristics of type III hyperlipoprot …
Apolipoprotein E polymorphism in American Indians and its relation to plasma lipoproteins and diabetes: The Strong Heart Study Academic Article ...
Following 12 weeks, in vitro aortic endothelial-independent relaxation was enhanced with both α-tocopherol and mixed-tocopherol (P , 0.05), while mixed-tocopherol enhanced aortic contraction at noradrenaline concentrations of 3 × 10−7 M to 3 × 10−5 M (P , 0.05), when compared to normal chow. Supplementation with α- and mixed-tocopherol reduced systemic concentrations of IL-6 (P , 0.001 and P , 0.001, respectively) and IL-10 (P , 0.05 and P , 0.001, respectively), while α-tocopherol also reduced MCP-1 (P , 0.05) and tumor necrosis factor (TNF)-α (P , 0.05). Aortic sinus plaque area was significantly reduced with α-tocopherol supplementation when compared to normal chow (P , 0.01 ...
Oxidative stress and inflammation are central mediators of atherosclerosis particularly in the context of diabetes. The potential interactions between the major producers of vascular reactive oxygen species (ROS), NADPH oxidase (NOX) enzymes and immune-inflammatory processes remain to be fully elucidated. In the present study we investigated the roles of the NADPH oxidase subunit isoforms, NOX4 and NOX1, in immune cell activation and recruitment to the aortic sinus atherosclerotic plaque in diabetic ApoE−/− mice. Plaque area analysis showed that NOX4- and NOX1-derived ROS contribute to atherosclerosis in the aortic sinus following 10 weeks of diabetes. Immunohistochemical staining of the plaques revealed that NOX4-derived ROS regulate T-cell recruitment. In addition, NOX4-deficient mice showed a reduction in activated CD4+ T-cells in the draining lymph nodes of the aortic sinus coupled with reduced pro-inflammatory gene expression in the aortic sinus. Conversely, NOX1-derived ROS appeared to ...
Apolipoprotein E (ApoE) is a multifunctional protein, and its deficiency leads to the development of atherosclerosis in mice. Patients with pulmonary hypertension (PH) have reduced expression of ApoE in lung tissue. ApoE is known to inhibit endothelial and smooth muscle cell proliferation and has anti-inflammatory and anti-platelet aggregation properties. Young ApoE-deficient mice have been shown to develop PH on high fat diet. The combined role of female sex and aging in the development of PH has not been investigated before. Here, we investigated the development of PH in young and middle-aged (MA) female ApoE-deficient mice and explored the role of exogenous estrogen (E2) replacement therapy for the aging females. Wild type (WT) and ApoE-deficient female mice (Young and MA) were injected with a single intraperitoneal dose of monocrotaline (MCT, 60 mg/kg). Some ApoE-deficient MA female mice that received MCT were also treated with subcutaneous E2 pellets (0.03 mg/kg/day) from day 21 to 30 after MCT
Apolipoprotein E (apoE) is critical in the modulation of cholesterol and phospholipid transport between cells of different types. Human apoE is a polymorphic protein with three common alleles, APO epsilon 2, APO epsilon 3, and APO epsilon 4. ApoE4 is associated with sporadic and late-onset familial Alzheimer disease (AD). Gene dose was shown to have an effect on risk of developing AD, age of onset, accumulation of senile plaques in the brain, and reduction of choline acetyltransferase (ChAT) activity in the hippocampus of AD subjects. To characterize the possible impact of the apoE4 allele on cholinergic markers in AD, we examined the effect of apoE4 allele copy number on pre- and postsynaptic markers of cholinergic activity. ApoE4 allele copy number showed an inverse relationship with residual brain ChAT activity and nicotinic receptor binding sites in both the hippocampal formation and the temporal cortex of AD subjects. AD cases lacking the apoE4 allele showed ChAT activities close or within ...
O:13:\PanistOpenUrl\:36:{s:10:\\u0000*\u0000openUrl\;N;s:6:\\u0000*\u0000idc\;N;s:6:\\u0000*\u0000fmt\;s:7:\journal\;s:6:\\u0000*\u0000doi\;s:0:\\;s:6:\\u0000*\u0000pii\;s:0:\\;s:7:\\u0000*\u0000pmid\;s:0:\\;s:9:\\u0000*\u0000atitle\;s:124:\Retroviral gene therapy in ApoE-deficient mice : ApoE expression in the artery wall reduces early foam cell lesion formation\;s:9:\\u0000*\u0000jtitle\;s:28:\Circulation (New York, N.Y.)\;s:9:\\u0000*\u0000stitle\;s:24:\Circulation (N. Y. N.Y.)\;s:7:\\u0000*\u0000date\;s:4:\1999\;s:9:\\u0000*\u0000volume\;s:2:\99\;s:8:\\u0000*\u0000issue\;s:2:\19\;s:8:\\u0000*\u0000spage\;s:4:\2571\;s:8:\\u0000*\u0000epage\;s:4:\2576\;s:8:\\u0000*\u0000pages\;s:0:\\;s:7:\\u0000*\u0000issn\;s:9:\0009-7322\;s:8:\\u0000*\u0000eissn\;s:0:\\;s:9:\\u0000*\u0000aulast\;s:5:\HASTY\;s:10:\\u0000*\u0000aufirst\;s:4:\A. ...
TY - JOUR. T1 - Avian and murine lr8b and human apolipoprotein E receptor 2. T2 - Differentially spliced products from corresponding genes. AU - Brandes, Christian. AU - Novak, Sabine. AU - Stockinger, Walter. AU - Herz, Joachim. AU - Schneider, Wolfgang J.. AU - Nimpf, Johannes. PY - 1997/6/1. Y1 - 1997/6/1. N2 - Apolipoprotein E-mediated lipid metabolism in the central nervous system plays an important role in cholesterol and phospholipid homeostasis of this organ, which is separated from the circulation by the blood-brain barrier. Moreover, in late-onset familial Alzheimer disease the frequency of the apolipoprotein E4 allele is significantly increased and the apoprotein is localized to extracellular plaques, one of the histological hallmarks of this disease. Recently, two distinct novel members of the low-density lipoprotein (LDL) receptor family, with the potential to bind apolipoprotein E and preferentially expressed in brain, have been characterized from human (D. Kim et al., 1996, J. ...
Rationale: A number of epidemiological studies have suggested an association of hyperhomocysteinemia (HHcy) and abdominal aortic aneurysm (AAA), but discrepancies exist. In addition, we lack direct evidence supporting a causal role.. Objective: We determined the association and contribution of HHcy to AAA formation.. Methods and Results: We first performed a meta-analysis of studies involving 1489 subjects and found a strong association of HHcy and AAA (odds ratio, 7.39). Next, we used angiotensin II-infused male apolipoprotein E-deficient mice and tested whether HHcy contributes to AAA pathogenesis. Homocysteine (Hcy) supplement (1.8 g/L) in drinking water resulted in mild HHcy. Intriguingly, HHcy greatly increased the incidence of angiotensin II-induced AAA and aortic dissection in apolipoprotein E-deficient mice (vehicle versus Hcy: 50% versus 100%; ...
Traffic related particulate matter air pollution is a risk factor for cardiovascular events; however, the biological mechanisms are unclear. We hypothesize that diesel exhaust (DE) inhalation induces up-regulation of inducible nitric oxide synthase (iNOS), which is known to contribute to vascular dysfunction, progression of atherosclerosis and ultimately cardiovascular morbidity and mortality. Methods: ApoE knockout mice (30-week) were exposed to DE (at 200 {mu}g/m{sup 3} of particulate matter) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week). iNOS expression in the blood vessels and heart was evaluated by immunohistochemistry and western blotting analysis. To examine iNOS activity, thoracic aortae were mounted in a wire myograph, and vasoconstriction stimulated by phenylephrine (PE) was measured with and without the presence of the specific inhibitor for iNOS (1400 W). NF-{kappa}B (p65) activity was examined by ELISA. The mRNA expression of iNOS and NF-{kappa}B (p65) was determined ...
The HDLs are responsible for the removal of free cholesterol from the blood. Low plasma levels of HDL are associated with increased cardiovascular risk. Low levels of HDL are frequently seen in patients with insulin resistance, from the metabolic syndrome to overt diabetes mellitus. Badimon et al. (59,60) elegantly demonstrated the antiatherogenic properties of HDL, reducing the number of fatty streaks and inducing disease regression in the rabbit experimental model. More recently, Rong et al. (61) evaluated the effects of HDL in advanced experimental atherosclerosis. Diseased thoracic aortic segments from hypercholesterolemic apolipoprotein E-deficient mice were transplanted in the abdominal aorta of apolipoprotein E-deficient mice not expressing (plasma HDL cholesterol approximately 26 mg/dl) or expressing (HDL approximately 64 mg/dl) a human apolipoprotein AI transgene. Mice with high plasma HDL showed significant changes in plaque composition, with macrophage area reductions ,80% and ...
In this study, the effect of the myxoma virus-derived serine protease inhibitor Serp-1 was investigated on de novo atherosclerosis and on advanced atherosclerotic lesions in apoE−/− mice equipped with a perivascular collar to induce carotid artery lesions.28 Serp-1 treatment led to a striking reduction in de novo lesion formation, whereas Serp-1 did not affect plasma total cholesterol and triglyceride levels as well as the total body weight of the animals or promote outward remodeling of the carotid artery. Plasma levels of Serp-1 after subcutaneous infusion remained constant during treatment at approximately 13.5 pmol/L. These low picomolar Serp-1 levels have been reported to suffice for effective serine protease inhibition and for blocking the hosts immune response to myxoma infection.20,21 Further gel filtration analysis revealed that Serp-1 was not degraded during the timeframe of the experiment. Blood cell levels did not differ between control and Serp-1 treatment groups, suggesting ...
Role of apolipoprotein E in neurodegenerative diseases Vo Van Giau,1 Eva Bagyinszky,1 Seong Soo A An,1 SangYun Kim2 1Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam, South Korea; 2Department of Neurology, Seoul National University College of Medicine in Seoul National Bundang Hospital, Seoul, South Korea Abstract: Apolipoprotein E (APOE) is a lipid-transport protein abundantly expressed in most neurons in the central nervous system. APOE-dependent alterations of the endocytic pathway can affect different functions. APOE binds to cell-surface receptors to deliver lipids and to the hydrophobic amyloid-β peptide, regulating amyloid-β aggregations and clearances in the brain. Several APOE isoforms with major structural differences were discovered and shown to influence the brain lipid transport, glucose metabolism, neuronal signaling, neuroinflammation, and mitochondrial function. This review will summarize the updated research progress on APOE functions
The human APOE gene, which codes for apolipoprotein E (apoE), has three major polymorphic alleles: ε2, ε3, and ε4 that give rise to amino acid substitutions. APOE-ε4 is a strong risk factor of sporadic Alzheimers disease (AD) but the reason why is still unknown despite intense research for more than 20 years. The aim of the study was to investigate if the concentrations of total apoE and the specific apoE isoforms in cerebrospinal fluid (CSF) differ between various neurodegenerative diseases and control individuals, as well as among the APOE genotypes. Quantification of total apoE and specific apoE isoforms (E2, E3, and E4) in CSF was performed using high-resolution parallel reaction monitoring mass spectrometry. In total, 1820 individuals were involved in the study including clinically diagnosed AD patients (n = 228), cognitively unimpaired (CU) patients (n = 896), and patients with other neurodegenerative disorders (n = 696). Follow-up data was available for 100 individuals, assessed at two time
BACKGROUND: Compared to the epsilon 2 or epsilon 3 alleles, the epsilon 4 allele of apolipoprotein E (ApoE4) is associated with twice the prevalence of late-onset Alzheimers disease (AD). Epidemiological studies show that risk of AD varies inversely with consumption of omega-3 fatty acids from fish and seafood. Despite apparently lower fish intake in AD, pooled analysis of the literature shows that plasma and brain docosahexaenoic acid (DHA) is actually the same in AD as in healthy age-matched controls. Fish oil trials in AD are also not convincing. We recently shown that ApoE4 carriers have 41% higher fasting plasma EPA and DHA compared to non-carriers, but the plasma EPA and DHA response to fish oil in ApoE4 carriers was half that seen in non-carriers.. HYPOTHESES: (i) Carriers of ApoE4 have altered metabolism of carbon-13 (13C)-DHA as well as EPA and DHA provided in a dietary supplement. (ii) A dietary supplement of EPA+DHA will improve cognitive performance but only in non-carriers of ...
Total silicon concentration of the aorta of female apoE knockout mice in Study 1 fed a diet high in butter fat and depleted in silicon, compared with mice fed t
Results from two small studies, involving a total of only 174 cases, have suggested that the increased risk of coronary heart disease conferred by cigarette smoking is substantially affected by genotype at the apolipoprotein E (APOE) epsilon2/epsilon3/epsilon4 polymorphism. We have established APOE genotypes in 4484 patients with acute myocardial infarction diagnosed before the age of 55 years for male and 65 years for female patients, and in 5757 controls with no history of cardiovascular disease. On average, the hazard ratio for myocardial infarction was 1.17 (95% CI 1.09-1.25; p|0.00001) per stepwise change from epsilon3/2 to epsilon3/3 to epsilon3/4 genotype. Among individuals in this study with known cigarette smoking status, the hazard ratio for myocardial infarction in smokers versus non-smokers was 4.6 (4.2-5.1). There was, however, no significant difference between the smoker/non-smoker hazard ratios for those with different APOE genotypes (chi2(2)=0.69; p=0.7). When differences in risk between
TY - JOUR. T1 - Lack of interleukin-1ß decreases the severity of atherosclerosis in apoE-deficient mice. AU - Kirii, Hirokazu. AU - Niwa, Tamikazu. AU - Yamada, Yasuhiro. AU - Wada, Hisayasu. AU - Saito, Kuniaki. AU - Iwakura, Yoichiro. AU - Asano, Masahide. AU - Moriwaki, Hisataka. AU - Seishima, Mitsuru. PY - 2003/4/1. Y1 - 2003/4/1. N2 - Objective - Atherosclerosis is considered to be a chronic inflammatory disease and many cytokines participate in the development of atherosclerosis, We focused on the role of interleukin-1β (IL-1β, one of the proinflammatory cytokines secreted by monocytes/macrophages, in the progression of atherosclerosis. Methods and Results - We generated mice lacking both apoE and IL-1β. The sizes of atherosclerotic lesions at the aortic sinus in apoE-/-/IL-1β-/- mice at 12 and 24 weeks of age showed a significant decrease of approximately 30% compared with apoE-/-/IL-1β+/+ mice, and the percentage of the atherosclerotic area to total area of apoE-/-/IL-1β-/- at 24 ...
AIMS: Vascular disease states are associated with endothelial dysfunction and increased production of reactive oxygen species derived from NADPH oxidases. However, it remains unclear whether a primary increase in superoxide production specifically in the endothelium alters the initiation or progression of atherosclerosis. METHODS AND RESULTS: Mice overexpressing Nox2 specifically in the endothelium (Nox2-Tg) were crossed with ApoE(-/-) mice to produce Nox2-Tg ApoE(-/-) mice and ApoE(-/-) littermates. Endothelial overexpression of Nox2 in ApoE(-/-) mice did not alter blood pressure, but significantly increased vascular superoxide production compared with ApoE(-/-) littermates, measured using both lucigenin chemiluminescence and 2-hydroxyethidium production (ApoE(-/-), 19.9 ± 6.3 vs. Nox2-Tg ApoE(-/-), 47.0 ± 7.0 nmol 2-hydroxyethidium/aorta, P| 0.05). Increased endothelial superoxide production increased endothelial levels of vascular cell adhesion protein 1 and enhanced macrophage recruitment in early
Genetic testing is not a new technology, in fact you may have had a genetic test as an infant. In the early 1960s genetic testing for phenylketonuria (PKU), a rare disorder of metabolism that if untreated will cause mental retardation, was introduced as a public health measure in the US. Genetic testing made PKU easy to spot and treatment of a strict diet regimen and further testing could begin right away. Today all 50 states have passed laws requiring that newborns be tested for PKU. The routine testing of newborns is currently the most widespread use of genetic testing.. ...
OBJECT: The presence of the apolipoprotein E-epsilon4 (APOE-epsilon4) allele is reported to be associated with poor outcome after traumatic brain injury (TBI). This study was performed to determine if the presence of the APOE-epsilon4 allele influenced outcome in a cohort of black patients with TBI
Objective ApoE can be an abundant component of chylomicron, VLDL, IDL, and HDL. and amino acid analyses. To evaluate the functional changes in VPO1-oxidized ApoE, lipid emulsion particle binding assays were employed. Results Oxidized ApoE binds weaker to lipid emulsion particles, which Rabbit polyclonal to PCBP1 mimic the large lipid complexes blood exhibited weaker clearance ability of plasma lipids. Conclusions Our data suggest that VPO1 is usually a new mediator regulating lipid homeostasis, implying a role in genesis and development of atherosclerosis. Introduction The physiological functions of lipoproteins are to transport lipids in blood and facilitate lipids through the cellular membrane into cells. Liver, intestine, and adipose tissue are the major tissues for metabolism and storage of lipids [1]. Bloodstream lipoproteins type five types of lipoprotein contaminants predicated on ultracentrifugation and electrophoresis, named high thickness lipoprotein (HDL), low thickness lipoprotein ...
Today more than 95 percent of experimental pathology research in atherosclerosis is carried out using the apo E knockout mouse. Not only has it provided a system for studying how lesions form in arteries, it also has given scientists a way to test the effects of other genes on how atherosclerosis develops, by breeding so-called candidate genes onto the apo E knockout mouse background. In addition, when Breslow crossed the apo E knockout trait onto different inbred mouse strains, he found a wide range in the size of the lesions that formed. This indicated modifier genes, and through genetic crosses he has found additional genes involved in atherosclerosis susceptibility. The apo E knockout mouse is also widely used in the pharmaceutical industry to test compounds for treating atherosclerosis. Jan L. Breslow received the AB from Columbia College (1963), the MA from Columbia University (1964), and the MD from Harvard Medical School (1968). After an internship and residency in pediatrics at Boston ...
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
Expression of Reg IV in inflammatory bowel disease and the predictive effect on lesion activity, Junwei Zhang, Jing Bai, Limin Zhang, Aibin Cheng
1. Gulani V, Calamante F, Shellock FG, Kanal E, Reeder SB. Gadolinium deposition in the brain: summary of evidence and recommendations. Lancet Neurol. 2017;16(7):564-570 doi:10.1016/S1474-4422(17)30158-8 2. World Health Organisation. WHO , Top 10 causes of death. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death. Published 2018. Accessed April 8. 2019 3. British Heart Foundation. BHF CVD STATISTICS COMPENDIUM 2017. 2017. 4. Bakhshi H, Meyghani Z, Kishi S. et al. Comparative Effectiveness of CT-Derived Atherosclerotic Plaque Metrics for Predicting Myocardial Ischemia. JACC Cardiovasc Imaging. 2019;12(7):1367-1376 doi:10.1016/j.jcmg.2018.05.019 5. Shen ZT, Zheng S, Gounis MJ, Sigalov AB. Diagnostic Magnetic Resonance Imaging of Atherosclerosis in Apolipoprotein E Knockout Mouse Model Using Macrophage-Targeted Gadolinium-Containing Synthetic Lipopeptide Nanoparticles. PLoS One. 2015;10(11):e0143453. doi:10.1371/journal.pone.0143453 6. Pan D, Caruthers SD, Senpan A, ...
Melanoma is the most aggressive skin cancer due to a propensity to metastasize and resistance to standard therapies. Nuclear hormone receptors are therapeutic targets in reproductive tissues, but their clinical utility in other solid tumors such as melanoma remains undefined. Pencheva and colleagues observed that liver-X nuclear hormone receptor β (LXRβ) was ubiquitously expressed across patient-derived melanoma cell lines and that LXR agonists inhibited invasion and endothelial cell recruitment of multiple melanoma cell lines in vitro in an LXRβ-dependent manner. Furthermore, oral administration of LXR agonists suppressed melanoma xenograft tumor growth, accompanied by a reduction in the number and size of tumoral endothelial vessels as well as lung and brain metastases. LXRβ is a known transcriptional activator of the metastasis suppressor apolipoprotein-E (ApoE), and extracellular ApoE was shown to be the primary mediator of tumor suppression by activated LXR, as antibody-mediated ...
Accumulation of β-amyloid (Aβ) in the brain is essential to Alzheimers disease (AD) pathogenesis. Carriers of the apolipoprotein E (APOE) ε4 allele demonstrate greatly increased AD risk and enhanced brain Aβ deposition. In contrast, APOE ε2 allele carries show reduced AD risk, later age of disease onset, and lesser Aβ accumulation. However, it remains elusive whether the apoE2 isoform exerts truly protective effect against Aβ pathology or apoE2 plays deleterious role albeit less pronounced than the apoE4 isoform. Here, we characterized APPSW/PS1dE9/APOE ε2-TR (APP/E2) and APPSW/PS1dE9/APOE ε4-TR (APP/E4) mice, with targeted replacement (TR) of the murine Apoe for human ε2 or ε4 alleles, and used these models to investigate effects of pharmacological inhibition of the apoE/Aβ interaction on Aβ deposition and neuritic degeneration. APP/E2 and APP/E4 mice replicate differential effect of human apoE isoforms on Aβ pathology with APP/E4 mice showing a several-fold greater load of Aβ plaques,
Introduction : The focus of this study was to assess cognitive functions in relation to androgens and specifically testosterone and dehydroepiandrosterone in postmenopausal women as well as the correlation between cognitive functions and these two androgens according to polymorphism of the...
The apolipoprotein E (APOE) gene exists in three isoforms in humans: APOE2, APOE3 and APOE4. APOE4 causes structural and functional alterations in normal brains, and is the strongest genetic risk factor of the sporadic form of Alzheimers disease (LOAD). Research on APOE4 has mainly focused on the neuronal damage caused by defective cholesterol transport and exacerbated amyloid-β and Tau pathology. The impact of APOE4 on non-neuronal cell functions has been overlooked. Astrocytes, the main producers of ApoE in the healthy brain, are building blocks of neural circuits, and Ca2+ signaling is the basis of their excitability. Because APOE4 modifies membrane-lipid composition, and lipids regulate Ca2+ channels, we determined whether APOE4 dysregulates Ca2+signaling in astrocytes. Ca2+ signals were recorded in astrocytes in hippocampal slices from APOE3 and APOE4 gene targeted replacement male and female mice using Ca2+ imaging. Mechanistic analyses were performed in immortalized astrocytes. Ca2+ fluxes were
RESULTS: We found that the most prevalent genotype was Apo Eε3/3, followed in order by Apo Eε3/4 and Apo Eε2/2. The estimated ApoE allelic frequencies in individuals with SD were 0.095, 0.560, and 0.345 for ε2, ε3, and ε4, respectively. In controls, the corresponding Apo E allelic frequencies were 0.146, 0.699, and 0.155. The percentage of ε4 allele carriers in SD group was significantly higher than that in control group ( ...
ABSTRACT. Alzheimer disease (AD) is a progressive and irreversible neurodegenerative disorder that is characterized by cognitive decline, memory loss and confusion. The E4 allele of the apolipoprotein E gene (APOE) is associated with AD and it is the main genetic risk factor for disease. Although the exact physiological function is unknown, bleomycin hydrolase (BLMH) may also be associated with AD development, although previous immunohistochemical findings have been inconsistent. Therefore, the purpose of this study was to evaluate the genotypic and allele frequencies of the APOE gene and BLMH 1450 G > A polymorphism and assess BLMH expression using PCR-RFLP and RT-qPCR analyses of blood samples from patients with Alzheimer disease (AD), healthy elderly adults (EC) and healthy young subjects (YC). BLMH expression was significantly different among groups (p = 0.015) and there was substantial reduction with age and with AD. The APOE and BLMH genotype frequency did not diverge from the ...
Methods Twenty wt C57BL/6J mice were chosen as the control group, and 60 ApoE−/− mice were randomly divided into three groups, ApoE−/− group, ApoE−/−+ IVIG group, ApoE−/−+ Simvastatin (Sm) group, with 20 mice in each group. Mice in ApoE−/−+IVIG group received an intraperitoneal injection of IVIG (1 mg/g) daily over a 5-day period prior to the exposure to high-fat diet. Mice in the ApoE−/−+Sm group received Sm (0.026 g/kg) per gavage for 10 weeks. Mice in C57 group and ApoE−/− group received PBS. Pathomorphological changes of aorta were observed by Masson staining evaluating plaques collagen content, immunohistochemical staining α-actin and CD68 evaluating contents of plaques vascular smooth muscle cells and macrophages, and oil red O staining evaluating plaques adipose tissue contents. FcγRIIIA expression changes in mice with atherosclerotic plaque were determined by assaying the protein level of membrane CD16 on monocytes using immunofluorescent staining and FACS ...
Emeto T, Seto SW, Golledge J. Targets for medical therapy to limit abdominal aortic aneurysm progress. Curr Drug Targets (2014) 15(9): 860-873. Wang Y, Emeto T, Lee J, Marshman L, Moran C, Seto SW, Golledge J. Mouse modes of intracranial aneurysm. Brain Pathology (2014) Accepted Manuscript.. Seto SW, Krishna SM, Moran CS, Liu D, Golledge J. Aliskiren limits abdominal aortic aneurysm, ventricular hypertrophy and atherosclerosis in an apolipoprotein E deficient mouse model. Clin Sci (Lond) (2014) 127(2): 123-34.. Wang Y, Seto SW, Golledge J. Angiotensin II, sympathetic nerve activity and chronic heart failure. Heart Failure Reviews (2014) 19(2): 187-198.. 2013. Clancy P, Seto SW, Koblar SA, Golledge J. Role of angiotensin converting enzyme 1/angiotensin II/ angiotensin receptor 1 axis in interstitial collagenase expression in human carotid atheroma. Atherosclerosis (2013) 229(2): 331-337.. Seto SW, Au AL, Poon CC, Zhang Q, Li RW, Yeung JH, Kong SK, Ngai SM, Wan S, Ho HP, Lee SM, Hoi MP, Chan SW, ...