The cardiocyte contractile dysfunction characteristic of pressure overload cardiac hypertrophy is accounted for to a remarkable degree by increased density of the cellular microtubule network (Tsutsui et al., 1993, 1994), which imposes a primarily viscous load on active myofilaments; that is, structural damping via intracellular frictional dissipation that impedes sarcomere shortening (Tagawa et al., 1997). This is accompanied by persistent increases in α- and β-tubulin on both the mRNA and protein levels (Tagawa et al., 1996). Thus, increased synthesis of αβ-tubulin heterodimers, effecting in turn microtubule formation, is one apparent cause for this greater microtubule density. Given, however, that the αβ-tubulin heterodimer-microtubule system is in dynamic equilibrium, enhanced microtubule stability is a second, and potentially synergistic, candidate mechanism for augmented microtubule density. This study was designed to evaluate this second potential mechanism.. The restriction of the ...

Although functions of MR in several other cell types have been elucidated in pathologic cardiac hypertrophy and heart failure,15-17,19,36-38 the roles of MR in T cells have not been illuminated. Through this study, we demonstrated that eplerenone and TMRKO attenuated POL-induced cardiac remodeling and dysfunction in parallel with attenuated cardiac inflammation, as well as decreased T-cell accumulation and activation in the heart. Moreover, in vitro results illustrated direct regulation of T-cell activation by MR.. This study implies that MR blockade in T cells is a feasible approach to treat pathologic cardiac hypertrophy and heart failure. MR deficiency in T cells was sufficient to suppress POL-induced cardiac hypertrophy, cardiac fibrosis, and cardiac dysfunction, as well as cardiac inflammation in mice. Particularly, TMRKO completely abrogated parts of the phenotype 1 week after POL, indicating that MR in T cells may be more important than MR in other cellular compartments in the early stage ...

The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc-induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam). Isolated working hearts and 13Carbon (13C )-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing 13C-labeled free fatty acids,more » acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. ...

Cardiac hypertrophy increases the risk of morbidity and mortality of cardiovascular disease and thus inhibiting such hypertrophy is beneficial. In the present study, we explored the effect of a bioactive peptide (PAP) on angiotensin II (Ang II)-induced hypertrophy and associated ventricular arrhythmias in in vitro and in vivo models. PAP enhances p21 activated kinase 1 (Pak1) activity by increasing the level of phosphorylated Pak1 in cultured neonatal rat ventricular myocytes (NRVMs). Such PAP-induced Pak1 activation is associated with a significant reduction of Ang II-induced hypertrophy in NRVMs and C57BL/6 mice, in vitro and in vivo, respectively. Furthermore, PAP antagonizes ventricular arrhythmias associated with Ang II-induced hypertrophy in mice. Its antiarrhythmic effect is likely to be involved in multiple mechanisms to affect both substrate and trigger of ventricular arrhythmogenesis. Thus our results suggest that Pak1 activation achieved by specific bioactive peptide represents a potential

Pathological cardiac hypertrophy is a complicated dynamic process that ultimately leads to heart failure. At present, we still have few effective methods to reverse pathological cardiac hypertrophy. Because the cardiovascular mortality increased 6- to 10-fold because of the development of pathological cardiac hypertrophy,21 it is of great importance to elucidate the underlying molecular mechanism of cardiac hypertrophy and discover potential target molecules to regulate pathological cardiac hypertrophy. Using genetic loss-of-function and gain-of-function animal models, the present study provides the systemic direct evidence that selective inhibition of GAS6 may be a therapeutic target for treating cardiac hypertrophy and congestive heart failure.. Mechanical stress and neurohormone stimuli are the 2 major causes for pathological cardiac hypertrophy.22 Both of these initially cause number of extracellular molecules to bind with their receptors and subsequently activate intrinsic signaling ...

Background: Extracellular matrix (ECM) molecules have been increasingly implicated in cardiac remodeling, and in particular the myocardial response to pressure overload. Podocan is a novel member of the small leucin-rich-repeat protein family of ECM proteins. We recently have characterized podocan as an inhibitor of the migration and proliferation of vascular smooth muscle cells. Now we are testing if podocan deficiency has an effect on pressure load-induced cardiac hypertrophy.. Methods and Results: We induced pressure overload cardiac hypertrophy using aortic banding (AB) in mice (age 10-12 weeks) with podocan-/- (n=6) and wild-type (WT) (n=7) genotype. Four weeks after AB, cardiac anatomy and function were assessed by echocardiography. In addition, histological analysis was used to assess the myocardial response to AB. Podocan-deficient mice showed significantly greater cardiac hypertrophy compared with WT mice after AB, whereas no significant differences were observed when comparing ...

Hypertensive cardiac hypertrophy (HCH) is a common cause of heart failure (HF), a major public health problem worldwide. However, the molecular bases of HCH have not been completely elucidated. Neuron-derived orphan receptor-1 (NOR-1) is a nuclear receptor whose role in cardiac remodelling is poorly understood. The aim of the present study was to generate a transgenic mouse over-expressing NOR-1 in the heart (TgNOR-1) and assess the impact of this gain-of-function on HCH. The CAG promoter-driven transgenesis led to viable animals that over-expressed NOR-1 in the heart, mainly in cardiomyocytes and also in cardiofibroblasts. Cardiomyocytes from TgNOR-1 exhibited an enhanced cell surface area and myosin heavy chain 7 (Myh7)/Myh6 expression ratio, and increased cell shortening elicited by electric field stimulation. TgNOR-1 cardiofibroblasts expressed higher levels of myofibroblast markers than wild-type (WT) cells (α 1 skeletal muscle actin (Acta1), transgelin (Sm22α)) and were more prone to ...

TY - JOUR. T1 - Parsing the roles of the transcription factors GATA-4 and GATA-6 in the adult cardiac hypertrophic response. AU - Van Berlo, Jop H.. AU - Aronow, Bruce J.. AU - Molkentin, Jeffery D.. PY - 2013/12/31. Y1 - 2013/12/31. N2 - The transcriptional code that programs cardiac hypertrophy involves the zinc finger-containing DNA binding factors GATA-4 and GATA-6, both of which are required to mount a hypertrophic response of the adult heart. Here we performed conditional gene deletion of Gata4 or Gata6 in the mouse heart in conjunction with reciprocal gene replacement using a transgene encoding either GATA-4 or GATA-6 in the heart as a means of parsing dosage effects of GATA-4 and GATA-6 versus unique functional roles. We determined that GATA-4 and GATA-6 play a redundant and dosage-sensitive role in programming the hypertrophic growth response of the heart following pressure overload stimulation. However, non-redundant functions were identified in allowing the heart to compensate and ...

Circulation. 2012 Oct 2;126(14):1705-16. doi: 10.1161/CIRCULATIONAHA.111.075978. Epub 2012 Aug 29. Research Support, N.I.H., Extramural

Cardiomegaly is a medical condition in which the heart is enlarged. It is more commonly referred to as an enlarged heart. The causes of cardiomegaly may vary. Many times this condition results from high blood pressure (hypertension) or coronary artery disease. An enlarged heart may not pump blood effectively, resulting in congestive heart failure. Cardiomegaly may improve over time, but many people with an enlarged heart need lifelong treatment with medications. Having an immediate family member who has or had cardiomegaly may indicate that a person is more susceptible to getting this condition. Cardiomegaly is not a disease but rather a condition that can result from a host of other diseases such as obesity or coronary artery disease. Recent studies suggest that cardiomegaly is associated with a higher risk of sudden cardiac death (SCD). Cardiomegaly is a condition affecting the cardiovascular system, specifically the heart. This condition is strongly associated with congestive heart failure. ...

The causes of cardiomegaly are not well understood and many cases of cardiomegaly are idiopathic (having no known cause). Prevention of cardiomegaly starts with detection. If a person has a family history of cardiomegaly, one should let ones doctor know so that treatments can be implemented to help prevent worsening of the condition. In addition, prevention includes avoiding certain lifestyle risk factors such as tobacco use and controlling ones high cholesterol, high blood pressure, and diabetes. Non-lifestyle risk factors include family history of cardiomegaly, coronary artery disease (CAD), congenital heart failure, Atherosclerotic disease, valvular heart disease, exposure to cardiac toxins, sleep disordered breathing (such as sleep apnea), sustained cardiac arrhythmias, abnormal electrocardiograms, and cardiomegaly on chest X-ray. Lifestyle factors which can help prevent cardiomegaly include eating a healthy diet, controlling blood pressure, exercise, medications, and not abusing alcohol ...

Background: Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. TLR2 is a member of the TLR family, and has been shown to recognize not only foreign substances, but also endogenous ligands, which induce inflammatory response called homeostatic inflammation. Recently, homeostatic inflammation has been revealed to contribute to the pathophysiology of various diseases. However, the role of homeostatic inflammation mediated by TLR2 on pressure overload-induced cardiac hypertrophy remains unclear.. Methods and Results: Pressure overload was induced in 8- to 12-week-old wild-type (WT) and TLR2 knock-out (KO) mice by transverse aortic constriction (TAC). In WT mice, TLR2 mRNA expression at 2 weeks after TAC was up-regulated compared with that after sham operation (1.32±0.18 versus 0.50±0.03, n=4, p=0.004). At 2 weeks after TAC, KO mice showed reduced cardiac hypertrophy and fibrosis with more left ventricular dilatation and impaired systolic function ...

cardiomegaly - MedHelps cardiomegaly Center for Information, Symptoms, Resources, Treatments and Tools for cardiomegaly. Find cardiomegaly information, treatments for cardiomegaly and cardiomegaly symptoms.

Here we observed that Pn contributes to the cardiac hypertrophic response, an observation that was not anticipated, given its primary function as an ECM cellular adhesion protein. That a cellular adhesion protein might affect the cardiac hypertrophic response is not without precedence, especially given the known importance of integrins in regulating cardiac reactive signaling4,35 and given the known role of Pn as a substrate for multiple combinations of integrins. For example, both focal adhesion kinase and integrin-linked kinase, which are intracellular signaling components of the integrin complex, function as important regulators of the cardiac hypertrophy response.36,37 Indeed, mice lacking the protein osteopontin, which is another cardiac inducible and secreted ECM protein that binds integrins, showed less pressure overload hypertrophy compared with wild-type mice.38 Based on these results, it is tempting to speculate that Pn alters the cardiac hypertrophic response by affecting signaling ...

Our findings presented herein have uncovered a previously unappreciated transcription factor pathway, mediated by HIF-2 in adipocytes, that plays a critical role in the regulation of adipocyte functions. Chronic activation of HIF-2, but not HIF-1, in adipocytes leads to adipose inflammation and pathological hypertrophy in the heart. The hypertrophic heart conditions presented by our mouse models are reminiscent of the cardiac hypertrophy observed in severely obese persons.2 Our solid genetic evidence strongly suggests that adipose hypoxia, observed under the condition of pathological obesity,5-7 may facilitate the development of obesity-related cardiac hypertrophy via sustained activation of HIF-2 in adipocytes.. Our findings demonstrate that HIF activation in adipocytes exerts its cardiac effects in a manner distinct from other purported mechanisms linked to obesity-associated cardiomyopathy. The pathological cardiomegaly observed herein occurs in the absence of lipid accumulation in blood ...

Speckle Tracking Based Strain Analysis Is Sensitive for Early Detection of Pathological Cardiac Hypertrophy. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.

TY - JOUR. T1 - Regulation of fetal gene expression in heart failure. AU - Dirkx, Ellen. AU - da Costa Martins, Paula A.. AU - De Windt, Leon J.. PY - 2013/12. Y1 - 2013/12. KW - Gene regulation. KW - Transcription factors. KW - Epigenetics. U2 - 10.1016/j.bbadis.2013.07.023. DO - 10.1016/j.bbadis.2013.07.023. M3 - Article. VL - 1832. SP - 2414. EP - 2424. JO - Biochimica et Biophysica Acta-Molecular Basis of Disease. JF - Biochimica et Biophysica Acta-Molecular Basis of Disease. SN - 0925-4439. IS - 12. ER - ...

Physiological cardiac growth occurs during postnatal development, and in response to long-term exercise training (15). This form of hypertrophy is associated with normal or enhanced cardiac function and normal cardiac structure. In contrast, pathological cardiac hypertrophy may arise as a compensatory mechanism against increased myocyte stress in many disease states. Any initial benefit is however overridden by eventual derangement of myocardial architecture and deterioration of function (15). Diabetic cardiomyopathy is characterized by adverse structural changes to the heart, including increased cardiac fibrosis (pathological in nature) and cardiomyocyte hypertrophy. Our results show that diabetes increased several markers of cardiomyocyte hypertrophy, including cardiomyocyte width as well as gene expression of β-myosin heavy chain, ANP, and BNP as previously described (13). No changes in heart weight-to-body weight or heart weight-to-tibia length ratios were observed in Ntg diabetic mice, ...

An abnormal enlargement of the heart; mild cardiomegaly is common in athletes. Cardiomegaly is a condition wherein the heart enlarges in a cardiothoracic ratio of more than 0.50. It can be attributed to a lot of causes, but mostly it is because of low heart output, otherwise referred to as a cardiac failure. A cardiothoracic ratio is the way to measure the size of a persons heart. In this case, cardiomegaly occurs if the heart is more than 50 percent bigger than the inner diameter of ones rib cage. Cardiomegaly is assumed to be the direct effect of the thickening of the heart muscles and that happens when the heart is given an increased workload. This increase workload on the other hand, may be due to other health conditions present in the body. Viral illnesses and previous heart attacks can cause the heart to overwork. Drug abuse, inflammation of the heart, and uncontrolled hypertension are the known issues that may give rise to cardiomegaly. ...

An abnormal enlargement of the heart; mild cardiomegaly is common in athletes. Cardiomegaly is a condition wherein the heart enlarges in a cardiothoracic ratio of more than 0.50. It can be attributed to a lot of causes, but mostly it is because of low heart output, otherwise referred to as a cardiac failure. A cardiothoracic ratio is the way to measure the size of a persons heart. In this case, cardiomegaly occurs if the heart is more than 50 percent bigger than the inner diameter of ones rib cage. Cardiomegaly is assumed to be the direct effect of the thickening of the heart muscles and that happens when the heart is given an increased workload. This increase workload on the other hand, may be due to other health conditions present in the body. Viral illnesses and previous heart attacks can cause the heart to overwork. Drug abuse, inflammation of the heart, and uncontrolled hypertension are the known issues that may give rise to cardiomegaly. ...

The mechanism for cardiac hypertrophy process that would be a benefit for improvement of cardiovascular endurance needed to be investigated throughly. Specific intensity of training may play a role for homeostasis process in cardiac during training. In the present study, we examine the effect of different intensity of treadmill training on cardiac hypertrophy process and autophagy related gene expression in male wistar rats. Three different intensities of treadmill training were conducted on 15 male wistar rats (Low Intensity: 10 m/minute, Moderate Intensity: 20 m/minute, and High Intensity: 30 m/minute) compared to 5 sedentary rats as control. Training duration was 30 min per day, frequency was 5 days per week, during 8 weeks period. Heart weight and heart weight/body weight ratio were measured after the experiments. Left ventricle myocardium was taken for microscopic analysis with HE staining. mRNA was extracted from left ventricle myocardium for examining αMHC and autophagy related gene expression

We found that hypertrophy induced secondary to pressure overload was significantly less in female WT mice compared with age-matched male WT mice at 2 wk postsurgery. We were therefore interested in determining whether this male/female difference was mediated via the ER and, if so, which receptor.. Direct effects of estrogen on the myocardium have been demonstrated (7, 14, 26), but the physiological roles of ER-α and ER-β in the myocardium remain largely unexplored. For the first time, we report the response of ERKO mice to pressure overload hypertrophy. We found that homozygous α-ERKO female mice exhibit a response to TAC that is identical to the response of WT females. This finding indicates that ER-α is not essential for the attenuation of the hypertrophic response. In contrast, we found that homozygous β-ERKO female mice subjected to TAC exhibited an increased degree of hypertrophy compared with WT female mice, comparable to WT males, indicating a role for ER-β in mediating an ...

The widespread use of the term hypertrophy to describe one or a few specific pathophysiological conditions is a holdover from the earliest scientific work on cardiac response to stress, in which cardiac enlargement was largely assumed to be the result of increased cardiomyocyte size and was qualitatively predictable based on the nature of the provocative stimulus.4 Hence, morphogenic changes in the heart were classified by the nature of the inciting hemodynamic stress as pressure-overload or volume-overload hypertrophy, referring to concentric hypertrophy (increased thickness of ventricular walls with little or no change in chamber volume) and eccentric hypertrophy (increased chamber volume with ventricular wall thickness increased in proportion with chamber dimensions), respectively. Note that, in both forms of hypertrophy, cardiac dry mass is increased. These etiologic/morphometric descriptors could be further categorized as compensated or decompensated, based on left ventricular ...

阿部 美保1, 福田 信夫2, 井形 次郎1, 稲山 久美1, 福田 保1, 篠原 尚典2, 添木 武2, 酒部 宏一2, 小野瀬 由紀子2, 田村 禎通2. Miho ABE1, Nobuo FUKUDA2, Ziro IKATA1, Kumi INAYAMA1, Tamotsu FUKUDA1, Hisanori SHINOHARA2, Takeshi SOEKI2, Kouichi SAKABE2, Yukiko ONOSE2, Yoshiyuki TAMURA2. 1公立学校共済組合四国中央病院内科, 2国立善通寺病院循環器科・臨床研究部. 1Depertment of Internal Medicine Shikoku Central Hospital, 2Division of Cardiology, and Clinical Research, Zentsuji National Hospital. キーワード : acute myocarditis, diastolic dysfunction of the ventricle, echocardiography, mitral annular velocity, left ventricular inflow velocity A man aged 27 years was admitted to the hospital because of fever and general fatigue. The electrocardiogram showed abnormal Q wave in leads II, III, and aVF, and poor R-wave progression in leads V3 through V6 at time of admission. The chest roentgenogram showed cardiac enlargement and no ...

Serotonin, in addition to its fundamental role as a neurotransmitter, plays a critical role in the cardiovascular system, where it is thought to be involved in the development of cardiac hypertrophy and failure. Indeed, we recently found that mice with deletion of monoamine oxidase A had enhanced levels of blood and cardiac 5-HT, which contributed to exacerbation of hypertrophy in a model of experimental pressure overload. 5-HT2A receptors are expressed in the heart and mediate a hypertrophic response to 5-HT in cardiac cells. However, their role in cardiac remodeling in vivo and the signaling pathways associated are not well understood. In the present study, we evaluated the effect of a selective 5-HT2A receptor antagonist, M100907, on the development of cardiac hypertrophy induced by transverse aortic constriction (TAC). Cardiac 5-HT2A receptor expression was transiently increased after TAC, and was recapitulated in cardiomyocytes, as observed with 5-HT2A in situ labeling by immunohistochemistry.

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What is the difference between Cardiomegaly and Cardiomyopathy? Cardiomegaly, the abnormal enlargement of heart, is a clinical manifestation of cardiomyopathies

An enlarged heart, or cardiomegaly, is a symptom of another medical condition it is not a. Physicians at the Mayo Clinic advise that patients with cardiomegaly get modest exercise, after. How to Reduce Estrogen in Men Through the Diet. Adherence to an appropriate diet and regular exercise. Diet should. Cardiomegaly. A nine pound weight loss was re-. vascular markings, and normal exercise tol erance without stridor. The patient. ale due to airway obstruction but without.

Yet not much is known about patients with PA, VSD at a cellular level, so any available new data for this group is taken along in the understanding of this disease. As mentioned earlier, we studied limited numbers of patients and controls. Therefore the conclusions can only be drawn with caution. It may be added here that the limited clinical data on normal myocardium in young healthy children is a limitation of our study as well. We are currently accumulating appropriate tissue biopsies to increase the number of contro ls. Two of these mutations are found within a troponin T binding site, located at amino acids 175 and 180. In this study, we analyze a transgenic mouse model for one of the mutations that occur at codon 180: a substitution of a glutami c acid for a glycine. These mice develop severe cardiac hypertrophy, substantial interstitial fibrosis, and have an increased heart weight! body weight ratio . Results show that calcium-handling proteins associated with the sarcoplasmic reticulum ...

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Disrupted organ growth leads to disease development. Hypertrophy underlies postnatal heart growth and is triggered after stress, but the molecular mechanisms involved in these processes are largely unknown.. Here we show that cardiac activation of p38γ and p38δ increases during postnatal development and by hypertrophy-inducing stimuli. p38γ/δ promote cardiac hypertrophy by phosphorylating the mTORC1 and mTORC2 inhibitor DEPTOR, which leads to its degradation and mTOR activation. Hearts from mice lacking one or both kinases are below normal size, have high levels of DEPTOR, low activity of the mTOR pathway and reduced protein synthesis. The phenotype of p38γ/δ−/− mice is reverted by overactivation of mTOR with amino acids, shRNA-mediated knockdown of Deptor, or cardiomyocyte overexpression of active p38γ and p38δ. Moreover, in WT mice, heart weight is reduced by cardiac overexpression of DEPTOR.. Our results demonstrate that p38γ/δ control heart growth by modulating mTOR pathway ...

Cardiac hypertrophic growth in response to pathological cues is associated with reexpression of fetal genes and decreased cardiac function and is often a precursor to heart failure. In contrast, physiologically induced hypertrophy is adaptive, resulting in improved cardiac function. The processes that selectively induce these hypertrophic states are poorly understood. Here, we have profiled 2 repressive epigenetic marks, H3K9me2 and H3K27me3, which are involved in stable cellular differentiation, specifically in cardiomyocytes from physiologically and pathologically hypertrophied rat hearts, and correlated these marks with their associated transcriptomes. This analysis revealed the pervasive loss of euchromatic H3K9me2 as a conserved feature of pathological hypertrophy that was associated with reexpression of fetal genes. In hypertrophy, H3K9me2 was reduced following a miR-217-mediated decrease in expression of the H3K9 dimethyltransferases EHMT1 and EHMT2 (EHMT1/2). miR-217-mediated, genetic, ...

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Tolerance of the canine heart to prolonged ischemic arrest was studied in 10 hearts from normal control dogs and 15 hearts from dogs with left ventricular hypertrophy (LVH); experiments were performed 1 year after banding the aorta in 8-week-old pupp

We present several noteworthy observations from our genetic deletion studies supporting the importance of PINK1 in the murine heart during postnatal development. In particular, PINK1−/− mice develop LV dysfunction with a reduced fractional shortening and evidence of pathological cardiac hypertrophy as early as 2 mo of age. Associated with this baseline cardiac phenotype we have shown that the PINK1−/− mice have higher degrees of cardiomyocyte apoptosis with fibrosis and reciprocal reduction in capillary density. In addition, the PINK1−/− mice have greater levels of oxidative stress as reflected by higher levels of lipid peroxidation, DNA damage, and decreased aconitase activity in conjunction with reduced activity of several cytoplasmic and mitochondrial antioxidative systems. In response to biomechanical stress, the PINK1−/− mice developed a further exaggeration in the degree of cardiac hypertrophy compared with their littermate controls. Of clinical relevance is the finding ...

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The discernment of gene expression changes at the molecular level presents great opportunities to conquer human disease; therefore it is important that...

Hypertension can lead to hypertrophic heart disease is a multi-factorial, multi-scale problem in which altered whole body hemodynamics and neurohormonal factors lead to a complex growth and remodeling response in the heart. The cells and extracellular matrix in the myocardium initially compensate to the abnormal environmental factors with altered gene expression, changes in contractile and mechanoenergetic function, cell and tissue structural remodeling, in turn further affecting circulatory dynamics and often leading to decompensation and failure. The goal of this project is to integrate novel cell signaling models of myocyte hypertrophy into organ-level continuum models of ventricular growth, remodeling and mechanoenergetics coupled to hemodynamic models of systemic hypertension, and validate these multi-scale models with experiments in rats subjected to ventricular hemodynamic overload and treated with drugs that target key response pathways. The resulting model systems will enable ...

The present study aimed to identify sex-differently expressed miRNAs in a late stage of hypertrophy (9 weeks) and the possible role of ERs in the regulation of these differences. Our previous studies identified ERbeta as an important determinant factor of the observed sex differences in pressure overload, playing different roles in males and females. This report identified a total of 30 miRNAs with sex and/or sex*surgery interaction effect 9 weeks after TAC in WT mice. The same effects were not observed in ERbeta-/- animals partially due to the higher expression of these miRNAs in ERbeta-/- females than in their WT counterparts. This study reveals a repression of a number of miRNAs by estradiol and its receptors alpha and beta in female cardiomyocytes, confirming the in vivo results and accentuating the important protective role of oestrogen and ERbeta in the female heart. Six of the miRNAs with sex differences in WT but not in ERbeta-/- hypertrophy models were found to be possible fibrosis ...

They asked themselves, how can something as commonplace and benign as a fruit extract reverse so many aspects of coronary artery disease, simultaneously, as it was evidenced by the study above? They say that the answer might be found in the fact that our ancestors evolved together with certain foods (fruits in particular) for so long that a lack of adequate quantities of these foods may directly result in deteriorating organ function. The journal Atherosclerosis published an interesting study in which they confirm that pomegranate extract may reverse or/and prevent the primary pathology associated with cardiac mortality: the accumulation of fatty materials on the coronary arteries known as atherosclerosis.What really surprised the researchers,were the other beneficial effects of the pomegranate extract treatment: Reduced lipid accumulation in the heart muscle Reduced ECG abnormalities Reduced levels of oxidative stress Reduced cardiac enlargement Reduced monocytie chemotactic protein-1, a ...

Notably, the Ang II-induced expression of hypertrophic hall marks had been also profoundly enhanced in Advertisement-FABP4-infected NRCMs compared with

Rationale Rescuing adverse myocardial redesigning can be an unmet clinical goal and, correspondingly, pharmacological opportinity for its meant reversal are urgently required. cardiac redesigning without influencing the vasculature. Increasing the arsenal of remodeling-reversing medicines to pathways apart from RAAS, a particular inhibitor of 11-hydroxy-steroid dehydrogenase type 1 (11 HSD1), an integral enzyme necessary for producing active glucocorticoids, completely rescued myocardial hypertrophy. This is connected with mitigating the hypertrophy-associated gene personal, including reversing the myosin weighty chain isoform change however in a design distinguishable from that connected with neovascularization-induced reversal. Conclusions Something was developed ideal for determining novel remodeling-reversing medicines operating in various pathways as well as for getting insights to their systems of actions, exemplified right here by uncoupling their vascular impacts. Introduction Cardiac ...

|i|Background and Objective|/i|. It has been reported that sodium ferulate (SF) has hematopoietic function against anemia and immune regulation, inflammatory reaction inhibition, inhibition of tumor cell proliferation, cardiovascular and cerebrovascular protection, and other functions. Thus, this study aimed to investigate the effects of SF on angiotensin II- (AngII-) induced cardiac hypertrophy in mice through the MAPK/ERK and JNK signaling pathways.|i| Methods|/i|. Seventy-two male C57BL/6J mice were selected and divided into 6 groups: control group, PBS group, model group (AngII), model + low-dose SF group (AngII + 10 mg/kg SF), model + high-dose SF group (AngII + 40 mg/kg SF), and model + high-dose SF + agonist group (AngII + 40 mg/kg SCU + 10 mg/kg TBHQ). After 7 d/14 d/28 days of treatments, the changes of blood pressure and heart rates of mice were compared. The morphology of myocardial tissue and the apoptosis rate of myocardial cells were observed. The mRNA and protein expressions of atrial

Detecting left atrial enlargement is frequently suspected in line with the presentation of signs and symptoms of the underlying cardiogenic condition. Once other tests addressing other complications are carried out to assist eliminate any potentially existence-threatening disorders, additional testing searching in the structure from the heart can be achieved to find out if left atrial enlargement exists.. Probably the most generally done test to identify left atrial enlargement is applying imaging methods known as echocardiograms. To control your emotions by utilizing seem waves to consider images of the center structures. Using other imaging tests, namely CT or MRI scans, may also be used to identify left atrial enlargement.. With respect to the underlying condition, treatment will normally follow. For instance, treating high bloodstream pressure calls for the effective use of bloodstream pressure medication for example beta-blockers and diuretics. Also, maintaining a healthy diet plan, ...

Noonan syndrome (NS) is caused by mutations in RAS/ERK pathway genes, and is characterized by craniofacial, growth, cognitive and cardiac defects. NS patients with kinase-activating RAF1 alleles typically develop pathological left ventricular hypertrophy (LVH), which is reproduced in Raf1L613V/+ knock-in mice. Here, using inducible Raf1L613V expression, we show that LVH results from the interplay of cardiac cell types. Cardiomyocyte Raf1L613V enhances Ca2+ sensitivity and cardiac contractility without causing hypertrophy. Raf1L613V expression in cardiomyocytes or activated fibroblasts exacerbates pressure overload-evoked fibrosis. Endothelial/endocardial (EC) Raf1L613V causes cardiac hypertrophy without affecting contractility. Co-culture and neutralizing antibody experiments reveal a cytokine (TNF/IL6) hierarchy in Raf1L613V-expressing ECs that drives cardiomyocyte hypertrophy in vitro. Furthermore, postnatal TNF inhibition normalizes the increased wall thickness and cardiomyocyte hypertrophy ...

Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played ...

Background- Inflammation remains a crucial factor for progression of cardiac diseases and cardiac hypertrophy remains an important cause of cardiac failure over all age groups. As a key regulator of inflammation, toll like receptor 4 (TLR4) plays an important role in pathogenesis of cardiac diseases. Being an important regulator of innate immunity, the precise pathway of TLR4 mediated cardiac complications is yet to be established. Therefore, the primary objective of the present study was to find the role of TLR4 in cardiac hypertrophy and the molecular mechanism thereof. Methods- Cardiac hypertrophy was induced with administration of isoproterenol (5mg/kg/day, sc). TLR4 receptor inhibitor RS-LPS (lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides; 5 microgram/day) and agonist LPS (Lipopolysaccharide from Escherichia coli; 3.12 microgram/day) were administered through osmotic pump along with isoproterenol. Cardiac hypertrophy as well as oxidative stress and mitochondrial

Angiotensin II (Ang II) is an important bioactive peptide in the renin‑angiotensin system, and it can contribute to cell proliferation and cardiac hypertrophy. Dysfunctions in transient receptor potential canonical (TRPC) channels are involved in many types of cardiovascular diseases. The aim of the present study was to investigate the role of the TRPC channel inhibitor SKF‑96365 in cardiomyocyte hypertrophy induced by Ang II and the potential mechanisms of SKF‑96365. H9c2 cells were treated with different concentrations of Ang II. The expression levels of cardiomyocyte hypertrophy markers and TRPC channel‑related proteins were also determined. The morphology and surface area of the H9c2 cells, the expression of hypertrophic markers and TRPC channel‑related proteins and the [3H] leucine incorporation rate were detected in the Ang II‑treated H9c2 cells following treatment with the TRPC channel inhibitor SKF‑96365. The intracellular Ca2+ concentration was tested by flow cytometry. ...

BACKGROUND:Despite its established significance in fibrotic cardiac remodeling, clinical benefits of global inhibition of TGF (transforming growth factor)-β1 signaling remain controversial. LRG1 (leucine-rich-α2 glycoprotein 1) is known to regulate endothelial TGFβ signaling. This study evaluated the role of LRG1 in cardiac fibrosis and its transcriptional regulatory network in cardiac fibroblasts. METHODS:Pressure overload-induced heart failure was established by transverse aortic constriction. Western blot, quantitative reverse transcription polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to evaluate the expression level and pattern of interested targets or pathology during fibrotic cardiac remodeling. Cardiac function was assessed by pressure-volume loop analysis. RESULTS:LRG1 expression was significantly suppressed in left ventricle of mice with transverse aortic constriction-induced fibrotic cardiac remodeling (mean difference, -0.00085 [95% CI, -0.0013 ...

Right ventricular hypertrophy is a heart disorder characterized by thickening of the walls of the right ventricle. Introduction. Cardiac hypertrophy refers to the cardiac remodeling process in response to a variety of intrinsic and extrinsic stimuli that stress the heart . Abstract Cardiac hypertrophy is the hearts response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress. Doxorubicin (DOX) is regarded as one of the most potent anthracycline antibiotic agents; however, its clinical usage has some limitations because it has serious … In this article I deal with only clinical aspects of LVH, because LVH is common, among all types of hypertrophies of the heart. HPE administration may thus be an effective approach to the treatment of cachexia, cardiac hypertrophy and fibrosis. This intervention study has the potential to discover a new strategy for the treatment of cardiac hypertrophy and fibrosis in patients on maintenance hemodialysis. Therefore, BA can ...

Supplementary MaterialsSupplementary Information 41598_2019_44331_MOESM1_ESM. in CACNA1H the denseness of DHPR and RyR2 clusters with pressure-overload cardiac hypertrophy and a rise in the denseness of SERCA2A proteins clusters. PLN proteins clusters reduced in denseness in 2-week TAC but came back to sham amounts Meptyldinocap by 4-week TAC. Furthermore, 2D-FFT evaluation revealed adjustments in molecular firm during pathological hypertrophy, with RyR2 and DHPR becoming dispersed while both SERCA2A and PLN sequestered into dense clusters. Our function reveals molecular adaptations that happen in important SR protein at an individual molecule during pressure overload-induced cardiomyopathy. Nanoscale modifications in proteins localization and patterns of manifestation of important SR proteins inside the cardiomyocyte offered insights in to the pathogenesis of cardiac hypertrophy, and particular proof that cardiomyocytes go through significant structural redesigning during the development of ...

Increasing evidence indicates that mitochondrial-associated redox signaling contributes to the pathophysiology of heart failure (HF). The mitochondrial-targeted antioxidant, mitoquinone (MitoQ), is capable of modifying mitochondrial signaling and has shown beneficial effects on HF-dependent mitochondrial dysfunction. However, the potential therapeutic impact of MitoQ-based mitochondrial therapies for HF in response to pressure overload is reliant upon demonstration of improved cardiac contractile function and suppression of deleterious cardiac remodeling. Using a new (patho)physiologically relevant model of pressure overload-induced HF we tested the hypothesis that MitoQ is capable of ameliorating cardiac contractile dysfunction and suppressing fibrosis. To test this C57BL/6J mice were subjected to left ventricular (LV) pressure overload by ascending aortic constriction (AAC) followed by MitoQ treatment (2 µmol) for 7 consecutive days. Doppler echocardiography showed that AAC caused severe LV

Background and Objectives: Type 2 diabetes is a risk factor for heart disease and has a major contribution in mortality due to cardiovascular diseases. In the present study, the effect of 12-week resistance training was investigated on cardiac hypertrophy, glucose, level, insulin, and insulin resistance index in STZ-induced diabetic rats. Methods: A total of ...

54 Downregulation Erb2 and Erb4 receptors in patients with congestive cardiomyopathy and in patients with pressure overload hypertrophy due to aortic stenosis is related to diastolic load. Delrue, L.; Bartunek, J.; Goethals, M.; De Bruyne, B.; De Beenhouwer, H.; Vanderheyden, M. // European Journal of Heart Failure. Supplements;Jun2004, Vol. 3 Issue 1, p12 An abstract of the study Downregulation Erb2 and Erb4 Receptors in Patients With Congestive Cardiomyopathy and in Patients With Pressure Overload Hypertrophy Due to Aortic Stenosis Is Related to Diastolic Load, by L. Delrue and colleagues is presented. ...

Circular RNA (circRNA) is a novel class of noncoding RNAs, and the roles of circRNAs in the development of cardiac hypertrophy remain to be explored. Here, we investigate the potential roles of circRNAs in cardiac hypertrophy. By circRNA sequencing in left ventricular specimens collected from 8-week-old mice with isoproterenol hydrochloride-induced cardiac hypertrophy, we found 401 out of 3323 total circRNAs were dysregulated in the hypertrophic hearts compared with the controls. Of these, 303 circRNAs were upregulated and 98 were downregulated. Moreover, the GO and KEGG analyses revealed that the majority of parental gene of differentially expressed circRNAs were not only related to biological process such as metabolic process and response to stimulus, but also related to pathway such as circulatory system and cardiovascular diseases. On the other hand, total 1974 miRNAs were predicted to binding to these differentially expressed circRNAs, and the possible target mRNAs of those miRNAs were also

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The heart initially compensates for hypertension-mediated pressure overload by enhancing its contractile force and developing hypertrophy without dilation. Gq protein-coupled receptor pathways become activated and can depress function, leading to cardiac failure. Initial adaptation mechanisms to reduce cardiac damage during such stimulation remain largely unknown. Here we have shown that this initial adaptation requires regulator of G protein signaling 2 (RGS2). Mice lacking RGS2 had a normal basal cardiac phenotype, yet responded rapidly to pressure overload, with increased myocardial Gq signaling, marked cardiac hypertrophy and failure, and early mortality. Swimming exercise, which is not accompanied by Gq activation, induced a normal cardiac response, while Rgs2 deletion in Gαq-overexpressing hearts exacerbated hypertrophy and dilation. In vascular smooth muscle, RGS2 is activated by cGMP-dependent protein kinase (PKG), suppressing Gq-stimulated vascular contraction. In normal mice, but not ...

In the current study, we used an experimental model of compensated cardiac hypertrophy induced by pressure overload over a 12-week period. The degree of hypertrophy induced in our study (136 ± 21%) was consistent with previous studies using the same model and reported a mean cardiac hypertrophy of 127%11 and 136%. 32 These authors reported noncardiac abnormalities associated with cardiac hypertrophy, including skeletal and diaphragmatic muscle abnormalities, without any physical signs of congestive heart failure, but they did not perform accurate evaluation of myocardial performance. 11 Our results showed a preserved state of contractility as indicated by the absence of significant difference in indexed Emaxbetween SHAM and LVH groups but an alteration of the diastolic compliance in the LVH group (fig. 1). These results explain significant differences in the inotropic and lusitropic baseline values between SHAM and LVH1groups. In the latter group, by altered diastolic compliance, the value of ...

Cardiac hypertrophy leading to heart failure remains a leading cause of morbidity and mortality in the 21st century despite major therapeutic advances. Improved understanding of novel molecular and cellular processes contributing to cardiac hypertrophy therefore continues to be important. Cyclin-dependent Kinase 9 (CDK9), part of a family of proteins controlling cell cycle and growth, has emerged as one such potential candidate over the last 5 years. CDK9 is the catalytic subunit of the CDK9/CyclinT complex and acts by phosphorylating the carboxy-terminal domain of RNA polymerase II. Hypertrophic signals, such as Endothelin-1 (ET-1) and phenylephrine, have been shown to cause CDK9 activation leading to a hypertrophic response in cultured mouse cardiomyocytes associated with reactivation of the foetal gene program. CDK9 also forms a complex with GATA4 to play a role in differentiation of mouse ES cells into cardiomyocytes. These findings suggest a specific role for CDK9 in controlling growth and ...

Cardiac hypertrophy is a thickening of the heart muscle - characterized by increased cell size rather than number - in response to conditions such as high blood pressure and coronary heart disease, which results in a decrease in size of the chambers of the heart, including the left and right ventricles. Since hypertrophy is associated with heart failure, irregular heart rhythms and an increased risk of angina and heart attack, understanding the mechanisms underlying this abnormal thickening is of great importance. Scientists at the Babraham Institute have now identified a new signalling process in the heart which contributes to cardiac hypertrophy. Rhythmical Ca2+ increases are fundamental to contraction of the heart muscle, but elevated Ca2+ levels also regulate the gene transcription that leads to hypertrophy. The Babraham team found that it is localised increases in Ca2+ concentrations in the cell nucleus that activate the genes responsible for hypertrophy. These nuclear Ca2+ signals, which ...

Heart disease has long been known as a frequent complicating factor and a common cause of exitus in acromegaly. Only nine years after the recognition of the features of acromegaly by Marie1 in 1886, Huchard2 reported cardiac enlargement in the clinical and autopsy findings of three patients with the disease. Fournier3 drew particular attention to the features of cardiac failure in a series of 25 patients, pointing out the frequent association of cardiomegaly with hypertrophy of all the viscera. Similar reports, consisting usually of one or two cases, have appeared from time to time in the French and German literature, ...

Four weeks of aortic banding resulted in significant hypertrophy in rats. This was evident from a significant increase in LVm/BW ratios. Furthermore, the hypertrophy was concentric in nature as evident from significant increases in the IVS and LVPW, an indication of increased septal and posterior wall thickness, respectively, at both systole and diastole. There was no change observed in LVID, an indication of increased chamber size, at systole and diastole. Results of the current study are consistent with results from our previous study (4). Treatment of aortic-banded rats with 2.5 mg·kg−1·day−1 resveratrol completely prevented development of hypertrophy because there was a normalization of the increase in left ventricle-to-body weight ratio. Resveratrol treatment also prevented concentric remodeling by normalizing IVS and LVPW at both systole and diastole. The beneficial effects of resveratrol in preventing PO-induced cardiac hypertrophy are consistent with another recent study, which ...

Inherited and acquired cardiomyopathy due to obesity and diabetes results in impaired lipid accumulation in the myocyte. Lipid accumulation in the heart leads t

September 29th is World Heart Day, that is held and arranged through the world heart foundation. The objective of this occasion would be to inform people about cardiovascular illnesses, which cause most cases of avoidable dying on the planet. To higher facilitate this purpose, weve compiled a summary of articles to assist enable you to get began on what causes cardiovascular disease. Youll find info on what can cause an enlarged heart and fluid round the heart, diabetes and cardiovascular disease, and what to anticipate throughout a massive cardiac arrest. Hopefully these details might help our readers and potentially save a existence later on.. Cardiomegaly (enlarged heart) isnt an illness by itself, but instead an indicator of some other condition. An enlarged heart is visible on X-ray images, but additional exams are needed to look for the exact reason for cardiomegaly.. Cardiomegaly could be temporary or chronic, based on its underlying cause. Oftentimes, cardiomegaly is really a ...

Their research, published in the Journal of Clinical Investigation, compared the differences between hypertrophic heart growth in rats as a result of exercise - which is beneficial - and heart growth induced by pathology - in this case increased load. Specifically, they compared epigenetic marks responsible for locking cells in their final developed state - important for preventing cells from switching to a less differentiated state. Notably for their analysis, the researchers employed a powerful cell sorting technique to allow them to study pure populations of heart muscle cells (cardiomyocytes) rather than a mix of all cell types in the heart - which, due to an alteration in composition during disease, would confound analysis ...

Over time, overloaded hearts typically become larger (a process called compensatory hypertrophy) to deal with the increased pressure. If prolonged, as occurs in untreated hypertension, the pressure overload leads to pathological hypertrophy and fibrosis, and ultimately leading to heart failure. Lauriol et al. found that mice with a cardiomyocyte-specific deficiency of RhoA, a GTP (guanosine 5′-triphosphate)-regulated protein, developed increased pathological hypertrophy but reduced fibrosis with chronic cardiac stress. These results suggest that targeting downstream effectors of RhoA, rather than RhoA itself, may be better for treating pathologies associated with heart failure.. ...

The term myocardial hypertrophy, say the working group, lacks precision. In cell biology the term hypertrophy describes growth via cell enlargement as opposed to growth by cell division, where hyperplasia is the correct term. Currently in cardiology the term hypertrophy is commonly applied to the situation in the whole heart where myocardial enlargement is accompanied by both hypertrophy and hyperplasia. In addition the term hypertrophy does not take account of the fact that non myocytes in the heart are not passive bystanders and also change in number when the heart remodels. Additionally there may be an invasion of inflammatory cells into the heart, and angiogenesis may occur.. The advantage of the term cardiac remodelling is that it simply defines reorganisation of the different cardiac tissue components, and can be used to describe an increase, or decrease in the size of the left ventricle, as well as a change to the cellular components, explained the first author of the paper, Ralph ...

To investigate whether apocynin, a NADPH oxidase inhibitor, produced cardioproteictive effects in Ang II-induced hypertensive mice, and to elucidate the underlying mechanisms. C57BL/6 mice were subcutaneously infused Ang II for 4 weeks to mimic

Dipeptidyl peptidase-4 (DPP-4) inhibitors are hypoglycemic agents. DPP-4 inhibitor has cardioprotective effects after transverse aortic constriction (TAC), but role of DPP-4 on cardiac fibrosis after TAC is not well known. Our aim was to determine the effects of DPP-4 on cardiac fibrosis in murine TAC model. Wild-type mice and DPP-4 knockout mice were subjected to TAC. Wild-type mice were then treated with vehicle or DPP-4 inhibitor. DPP-4 activities in serum and heart tissue were significantly increased at 2 weeks after TAC, but they were significantly decreased by DPP-4 inhibitor treatment ...

Signs or symptoms hematomacrosis - What are the symptoms of hemochromatosis? Varies. Many times, it is only presented with high iron saturation and or iron storage without having any symptoms. However, the clinical manifestations of iron accumulation can include liver disease, elevation of liver enzymes, skin pigmentation, diabetes mellitus, arthropathy, impotence in males, and cardiac enlargement with or without heart failure or conduction defects etc.

Although cardiac hypertrophy is an important condition that usually precedes heart failure (Carreno et al., 2006), there are limited reports of altered expression of P450 genes during cardiac hypertrophy. The expression of P450 has been studied in SHRs as compared with SD rats (Thum and Borlak, 2002) and the expression of sEH has been studied in spontaneously hypertensive heart failure (SHHF) rats as compared with normal strains (Monti et al., 2008). Nevertheless, there are no data about the effect of experimentally induced cardiac hypertrophy on the expression of P450 and sEH genes and their associated P450-derived metabolites of AA. To the best of our knowledge, this work demonstrates for the first time the effect of experimentally induced cardiac hypertrophy on the expression of several P450 genes and P450-dependent AA metabolism in rats. In addition, the current study demonstrates the tissue-specific expression of many P450 genes and sEH in male SD rats.. Tissue-specific expression of P450 ...

Therapeutic inhibition of the miR-34 family (miR-34a -b -c) or miR-34a only have emerged as encouraging strategies for the treating cardiac pathology. safety this approach will probably result in much less potential off-target results. Subsequently silencing of miR-34a only may be inadequate in configurations of founded cardiac pathology. We lately proven Cobicistat that inhibition from the miR-34 family members however not miR-34a only provided benefit inside a chronic style of myocardial infarction. Inhibition of miR-34 also attenuated cardiac redesigning and improved center function pursuing pressure overload nevertheless silencing of miR-34a only was not analyzed. The purpose of this research was to assess whether inhibition of miR-34a could attenuate cardiac redesigning inside a mouse model with pre-existing pathological hypertrophy. Mice had been put through pressure overload via constriction from the transverse aorta for a month and echocardiography was performed to verify remaining ...