This study will investigate the effects of vildagliptin compared with glimepiride on vascular endothelial function in patients with type 2 diabetes mellitus.
This study investigated the effect of sitagliptin and vildagliptin (DPP-4 Inhibitor) on vascular endothelial function in Type 2 Diabetes Mellitus patients.
To the best of our knowledge, the present study is the largest to compare the effect on endothelial function, assessed by FMD, of different types of exercise training in post-myocardial infarction patients. Several interesting findings emerged from our trial.. First, in accordance with previous reports,19,24 an important degree of endothelial dysfunction (assessed by FMD) was found in a large, homogeneous group of patients 3 weeks after an acute myocardial infarction. In fact, the mean percent FMD was significantly inferior (4.2%) to a value considered normal in healthy subjects (≈10%).22. Second, in line with previous results,7,19 exercise helped to restore endothelial function as shown by the improvement in indexes of systemic endothelial function in all trained patients, whereas no significant changes in endothelium-independent vasodilatation were apparent. This adaptation appears to be predominantly endothelium dependent9; in fact, exercise increases shear stress, which is a strong ...
Endothelial cell dysfunction has been extensively associated with hypercholesterolemia and atherogenesis. However, most of the early work relevant to endothelial vascular function has focused on large conduit vessels (eg, the aorta, iliac arteries, large coronary arteries, etc), which are common sites of atherosclerotic lesions but are not generally involved in the direct regulation of tissue perfusion. Conversely, the microvasculature regulates tissue perfusion but does not usually develop overt atherosclerosis. Nevertheless, studies of the microvascular endothelium may be of importance in assessing the overall cardiovascular effect of atherosclerosis because it may represent an early marker of atherogenesis. Thus, endothelial function may be abnormal in this segment of the circulation, despite the absence of lesions in larger vessels in the setting of hyperlipidemia and atherosclerosis. In the present article, we have shown that 1-week administration of a 0.5% cholesterol diet to rabbits ...
Aging stem cells may play a critical role in determining the effects of aging on organ function. With regard to vascular diseases, it has been postulated that circulating EPCs are involved in the repair mechanisms after endothelial damage (27,28). Ultimately, deterioration of endothelial or vascular function may be related to both quantitative and qualitative changes of stem cells.. We describe here the first comprehensive analysis of the association between age-related endothelial dysfunction and the number and function of circulating EPCs, defined by expression of CD34+/VEGFR2+ and CD133+/VEGFR2+. Although no quantitative differences in EPCs were observed, our data illustrate that culture-enriched EPCs from old but otherwise healthy subjects are impaired in terms of fundamental functional features like proliferation (important for amplifying the cellular pool), migration (critical for homing of circulating EPCs), and survival. We demonstrate a significant univariate correlation between the ...
Our work identifies AMPKα1 as a new kinase that phosphorylates Ser188 of RhoA and establishes a novel signaling cascade induced by estradiol. In VSMC, ER stimulation by E2 activates AMPK that phosphorylates RhoA thereby reducing Rho-Rock signaling pathway activity and limiting vasoconstriction. Our results also demonstrate that AMPKα1-RhoA pathway is constitutively active in female mice and could thus participate to the vasoprotective effect of estrogens.. AMPK is an ubiquitous heterotrimeric serine/threonine protein kinase activated by pathological stimuli, such as oxidative damage, osmotic shock, hypoxia, and glucose deprivation, as well as by physiological stimuli such as exercise and muscle contraction, and by hormones including leptin and adiponectin.27 In general, AMPK is activated in response to decreased cellular energy charge (increased in AMP/ATP ratio) and regulates carbohydrate and lipid metabolism.28-30 Although there is a robust correlation between the activity of the AMPK and ...
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Fingerprint Dive into the research topics of Mathematical modeling of vascular endothelial cell layer maintenance: the role of endothelial cell division, progenitor cell homing and telomere shortening. Together they form a unique fingerprint. ...
The study of endothelial cells has provided unique insight into important cardiovascular diseases and the control of angiogenesis during tumour development. The control of new blood vessel formation, or angiogenesis, is orchestrated by vascular endothelium and endothelial cells respond to unique signals in their environment with a repertoire of cellular and molecular responses. Studies directed towards dissecting the molecular mechanisms underlying alterations in genotype and phenotype are underway using prototypic endothelial cell gene products (e.g. endothelin-1, eNOS, CXCR4, adhesion molecules such as VCAM-1 or ICAM-1) and exciting models of cellular activation (hypoxia, shear stress and epigenetic modifiers). An excellent example of the applicability of this approach is our finding that shigatoxins, bacterial-derived exotoxins that cause severe inflammation of capillary beds in patients with E coli 0157:H7, regulate the expression of genes in vascular endothelium at the post-transcriptional ...
This prospective study demonstrated that impaired FMD of the brachial artery is a strong independent predictor of cardiovascular events in patients with peripheral arterial disease. The predictive value of FMD was independent of the extent of reactive hyperemia and the response to an exogenous source of nitric oxide (NTG), suggesting that the findings are not due to variation in the stimulus for vasodilation or the function of vascular smooth muscle. Thus, the study supports a pathophysiologic link between endothelial dysfunction and cardiovascular events.. Previous invasive coronary studies examined the relation between endothelial dysfunction and cardiovascular risk. During a 28-month follow-up of 157 patients, Suwaidi et al. (3)demonstrated that coronary endothelial dysfunction in the absence of obstructive lesions was associated with increased cardiovascular events. Schachinger et al. (4)reported that impaired vasodilator responses to both endothelium-dependent and -independent agonists ...
Clinical assessment of endothelial function involves the measurement of dilation of conductance arteries during periods of acute increases in shear stress, believed to be almost entirely mediated by NO release, or measurement of agonist-induced vasodilation.1-3 The magnitude of endothelial dysfunction is an important and independent predictor of future development of cardiovascular risk factors, such as hypertension and diabetes, and of cardiovascular events.4-8 Thus, assessment of endothelial function quantifies subclinical vascular damage and is a valuable prognostic tool.3,4 The available clinical techniques for estimating endothelial function require substantial expertise and are not suitable for use in routine clinical practice. There is, thus, a critical need for simpler tests, potentially biomarkers, that would provide an accurate index of vascular endothelial function.. The bioavailability of NO from the vascular endothelium is exquisitely modulated by reactive oxygen species that ...
Endothelium plays a critical role in maintaining healthy homeostatic properties of the vasculature. Endothelial dysfunction promotes atherosclerosis by creating a vasospastic, prothrombotic, and proinflammatory milieu. Therefore, the assessment of endothelial function as a surrogate marker of arterial health has gained significant interest for clinical risk assessment beyond the risk conveyed by a structural impediment to flow (1). Furthermore, the observation that cardiovascular events may occur remotely from the site in which the endothelial dysfunction is detected prompted clinical studies in search for peripheral vascular endothelial dysfunction as a predictor of cardiovascular events.. Endothelial dysfunction is characterized by a paradoxical vasoconstriction or attenuated dilation due to reduced endothelium-dependent nitric oxide (NO) release. In earlier studies, the response of the epicardial arteries to infused acetylcholine was measured invasively to assess endothelial function in the ...
The endothelium is the lining of our arteries and consists of a single layer of tile-like cells. The endothelium is central to artery health and disease. Anything that compromises the health of the endothelium has an immediate effect on the flow of blood to every organ. Atherosclerosis, the obstruction of arteries by cholesterol, is merely the end result of repeated endothelial damage. Every fat and cholesterol laden meal causes an inflammatory storm within the arteries that lasts for many hours and has a measureable effect on endothelial function.. Endothelial cells are continually releasing nitric oxide and many other chemical messengers that control blood flow and blood clotting. Nitric oxide (NO) is the key player. It diffuses into the muscular layer of the artery wall and causes the muscle cells to relax a little. The physics of pipes and fluids dictates that a small increase in the diameter of the vessel results in a big increase in blood flow. This provides for minute to minute adjustment ...
Ventricular hypertrophy following chronic overload results from the hypertrophy of cardiomyocytes and the hyperplasia of non muscle cells in the
Endothelial dysfunction has been implicated in the pathological process of coronary artery disease as well as an adverse event after coronary drug eluting stent (DES) implantation. In this review, an overview will be given of the evidence to date regarding the effects of coronary DES on endothelial function obtained from both clinical and experimental studies. Stenting in general and DES seem to impair several aspects of endothelial function: provision of a permeable barrier function; modulation of adhesion, thrombosis and inflammation; and regulation of vascular tone. However, new insights show that the effects of DES can extend beyond the stent and peri-stent area: the vascular bed distal to the stent, starting with the distal conduit vessels up to the distal microvasculature, might be at risk. In addition, insight into the mechanism of DES induced endothelial dysfunction has been gained. To finalize this review, clinical complications and solutions of DES associated endothelial dysfunction ...
There are several invasive and noninvasive methods available to the clinical researcher for the assessment of endothelial function. The first investigations in humans involved invasive pharmacological vascular function testing, which have been used to gain a detailed understanding of the mechanisms involved in the pathogenesis of endothelial dysfunction and atherosclerosis as well as novel targets for intervention. Techniques for endothelial function testing have evolved over time from these invasive methods, which, by their nature, are restricted to small studies in the research laboratory, to more standardized noninvasive methods, which are suitable for use in large prospective cohort studies and clinical trials. This paper describes currently available methods for assessment of endothelial function and their potential application in cardiovascular research and clinical practice.
Background: While diabetes is associated with diminished vascular NO levels, the precise mechanisms of diabetic endothelial dysfunction are not known. We hypothesized that deficient eNOS S1179 phosphorylation plays a key role in diabetic vascular abnormalities, and that increasing S1179 phosphorylation may improve endothelial function. To test this hypothesis, we created eNOS knock-in mice that carry a S1179D mutation in the eNOS gene, resulting in the generation of a phosphomimetic form of eNOS with increased enzymatic activity and NO generation. We bred these animals to db/db mice to obtain S1179D-db/db mice to test whether modulation of the S1179 phosphorylation site could overcome diabetic vascular dysfunction, and whether this could affect stroke size in vivo.. Experimental Procedures: Adult male mice were anesthetized by 30 % oxygen, 70 % nitrous oxide, and 1.5 % isoflurane. Body temperature was maintained at 36-37°C. Vessel reactivity studies were performed on isolated pressurized ...
The results of our prospective study clearly demonstrate that endothelial function significantly influences the future development of diabetes, independently of age and several other well-known diabetes risk factors. In our opinion, this is a very important tool because it radically changes the way endothelial dysfunction is considered. Endothelial dysfunction is usually explained as being the consequence of the endothelium being exposed to damaging factors, e.g., high blood pressure, high cholesterol, high blood glucose, smoking, etc.-the response-to-injury theory (3). Our data revolutionize the concept because they indicate that endothelial dysfunction may influence the development of diabetes. The present results have been obtained by studying a population of postmenopausal women who represent a unique model of studying endothelial dysfunction consequences. In fact, the decrease in estrogens that physiologically follows menopause does in itself compromise the endothelial function in women, ...
Vascular endothelium provides a selective barrier between the blood and tissues, participates in wound healing and angiogenesis, and regulates tissue recruitment of inflammatory cells. Nuclear factor (NF)- \(\kappa\)B transcription factors are pivotal regulators of survival and inflammation, and have been suggested as potential therapeutic targets in cancer and inflammatory diseases. Here we show that mice lacking IKK\(\beta\), the primary kinase mediating NF-\(\kappa\)B activation, are smaller than littermates and born at less than the expected Mendelian frequency in association with hypotrophic and hypovascular placentae. IKK\(\beta\) -deleted endothelium manifests increased vascular permeability and reduced migration. Surprisingly, we find that these defects result from loss of kinase-independent effects of IKK\(\beta\) on activation of the serine-threonine kinase, Akt. Together, these data demonstrate essential roles for IKK\(\beta\) in regulating endothelial permeability and migration, as ...
Despite its known expression in both the vascular endothelium and the lung epithelium, until recently the physiological role of the adhesion receptor Gpr116/ADGRF5 has remained elusive. We generated a new mouse model of constitutive Gpr116 inactivation, with a large genetic deletion encompassing exon 4 to exon 21 of the Gpr116 gene. This model allowed us to confirm recent results defining Gpr116 as necessary regulator of surfactant homeostasis. The loss of Gpr116 provokes an early accumulation of surfactant in the lungs, followed by a massive infiltration of macrophages, and eventually progresses into an emphysemalike pathology. Further analysis of this knockout model revealed cerebral vascular leakage, beginning at around 1.5 months of age. Additionally, endothelial-specific deletion of Gpr116 resulted in a significant increase of the brain vascular leakage. Mice devoid of Gpr116 developed an anatomically normal and largely functional vascular network, surprisingly exhibited an attenuated ...
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The thin layer of cells that lines the interior of blood vessels, known as the endothelium, plays a complex role in vascular biology. The endothelium mediates blood vessel tone, hemostasis, neutrophil recruitment, hormone trafficking, and fluid filtration. Endothelial dysfunction, as defined by a lack of NO, has been linked to a variety of disease states, including atherosclerosis, diabetes mellitus, coronary artery disease, hypertension, and hypercholesterolemia. Indeed, restoration of endothelial function is one of the earliest recognizable benefits of statin therapy. In 1995, James Liao and colleagues published a study in the ...
A discovery arose from growing human arterial endothelial cells in the lab, and scientists from the Morgridge Institute for Research couldn’t be more
The present invention relates to intercellular adhesion inhibitory factors produced by cytokine activated endothelial cells. These factors designated endothelial-derived IL-8 find use in the diagnosis and treatment of inflammation and in the protection of endothelial cells from neutrophil mediated damage.
In normal vascular physiology, nitric oxide (NO) plays a key role in maintaining the vascular wall in a quiescent state by inhibition of inflammation, cellular proliferation, and thrombosis (1). What is generally referred to as endothelial dysfunction should more appropriately be considered endothelial activation. Such activation may be beneficial to humans in certain instances, such as during infection, and harmful in others, such as during obesity.. During infection, a reduction in NO may allow for activation of endothelial expression of chemokines, cytokines, and adhesion molecules, designed to recruit and activate leukocytes and platelets. Endothelial activation (endothelial dysfunction) may be considered as a beneficial and physiological response to infection.. In the absence of an active infection, most cardiovascular risk factors (smoking, elevated lipids, hypertension, aging) reduce NO bioavailability-a maladaptive response that sets the stage for the development of atherosclerosis. The ...
My laboratory is interested in bi-directional crosstalk between vascular endothelium and cardiomyocytes that regulates cardiac size and function. As an alternative to myocyte-driven hypertrophy in response to hemodynamic stress we recently reported a cross-talk loop induction of myocardial hypertrophy by expanding vascular endothelium in the absence of traditional hypertrophy stimuli. This reveals a new and unexplored role played by the endothelium in regulation of adult organ growth and size that would be of great interest in formulating new therapeutic angiogenic approaches to the treatment of heart disease.. Our hypothesis is that an increase in vascular endothelium in the adult heart results in increased nitric oxide (NO) production that in turn drives the growth of cardiomyocytes by sustained ubiquitination of the negative regulator of G protein signaling subtype 4 (RGS4) and derepression of the hypertrophic program via heterotrimeric G protein signaling. To investigate this crosstalk we ...
Endothelium helps in maintaining vascular tone by regulating the vascular permeability. It selectively allows only certain molecules to cross the endothelial barrier. A large number of micro and macro vascular complications are associated with endothelial dysfunction in diabetes including cardiovascular disease, stroke and peripheral vascular diseases. Moreover, a series of
Fingerprint Dive into the research topics of Evidence for vasculoprotective effects of ET,sub,B,/sub, receptors in resistance artery remodeling in diabetes. Together they form a unique fingerprint. ...
The vascular endothelium comprises a dynamic interface with the blood and acts as an integrator and transducer of both biochemical (e.g. inflammatory cytokines)...
When the endothelial cells get affected, the walls of the arteries tend to lose their elasticity thereby becoming hard and thick. Many studies in the cardiovascular field point out that endothelial dysfunction is the clinical manifestation of cardiovascular disease.
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Endothelial dysfunction has been shown to be of significance in predicting stroke and heart attacks due to the inability of the arteries to dilate fully.
TY - JOUR. T1 - Endothelium removal augments endothelium-independent vasodilatation in rat mesenteric vascular bed. AU - Iwatani, Y.. AU - Kosugi, K.. AU - Isobe-Oku, S.. AU - Atagi, S.. AU - Kitamura, Yoshihisa. AU - Kawasaki, H.. PY - 2008/5. Y1 - 2008/5. N2 - Background and purpose: The vascular endothelium regulates vascular tone by releasing various endothelium-derived vasoactive substances to counteract excess vascular response. We investigated whether the vascular endothelium regulates vasodilatation via released endothelium-derived contracting factors (EDCFs), by examining the effect of endothelium removal on responses to periarterial nerve stimulation (PNS) and various vasodilator agents. Experimental approach: The rat mesenteric vascular bed was perfused with Krebs solution. Vasodilator responses to PNS and 5 min perfusion of vasodilator agents in preparations with endothelium were compared with those in the same preparations without endothelium. The endothelium was removed by 30 s ...
Atrial natriuretic peptide (ANP), a hormone considered to be an important regulator of intravascular fluid volume, has been shown to bind specifically to receptors on endothelial cells. In this study, the role of ANP-specific binding was investigated by examining the effect of ANP on the morphology and macromolecular permeability of monolayer cultures of bovine aortic endothelial cells (BAEC). ANP alone (10-9 -10-6 M) had no observable effect on the morphology of the monolayers. However, incubation of the endothelial monolayers with ANP (10-8 -10-6 M) antagonized the characteristic thrombin-induced (1 unit/ml) cell shape changes and the formation of intercellular gaps. Since chemically and enzymatically generated oxidants have also been shown to alter endothelial cell shape and increase macromolecular permeability, the effect of ANP on oxidant-induced injuries was investigated. Treatment of endothelial monolayers with glucose oxidase (1.4 unit/ml) elicited changes in cell shape characterized by ...
TY - JOUR. T1 - Regulation of vascular endothelial barrier function by Epac, a cAMP-activated exchange factor for Rap GTPase. AU - Cullere, Xavier. AU - Shaw, Sunil K.. AU - Andersson, Lorna. AU - Hirahashi, Junichi. AU - Luscinskas, Francis W.. AU - Mayadas, Tanya N.. PY - 2005/3/1. Y1 - 2005/3/1. N2 - Endothelial cell-cell junctional proteins and cortical actin are of central importance for regulating vascular permeability. Rap1, a member of the Ras family of GTPases, is enriched at endothelial cell-cell contacts and activated by cyclic AMP (cAMP) through a PKA-independent pathway. Activation of a cAMP-inducible gua nine-exchange factor for Rap, Epac, results in markedly enhanced basal endothelial barrier function by increasing cortical actin and subsequent redistribution of adherens and tight junctional molecules to cell-cell contacts. Activation of Epac also counteracts thrombin-induced hyperpermeability through down-regula tion of Rho GTPase activation, suggesting cross-talk between Rap and ...
TY - JOUR. T1 - Thrombin-induced gap formation in confluent endothelial cell monolayers in vitro. AU - Laposata, Michael. AU - Dovnarsky, D. K.. AU - Shin, H.. PY - 1983. Y1 - 1983. N2 - When thrombin is incubated with confluent monolayers of human umbilical vein endothelial cells in vitro, there is a change in the shape of the endothelial cells that results in gaps in the monolayer disrupting the integrity of the endothelium and exposing the subendothelium. Using a grid assay to measure this phenomenon, we observed that up to 80% of the surface area once covered by cells was uncovered after a 15-min incubation with 10-2 U/ml (10-10 M) thrombin. The effect was apparent within 2 min and did not remove cells from the surface of the culture dish. The gaps in the monolayer completely disappeared within 2 hr after exposure to thrombin. The effect of thrombin was inhibited by preincubation of thrombin with hirudin or antithrombin III plush heparin or by preincubation of the monolayers with dibutyryl ...
Endothelial activation is an integral component of inflammatory rheumatic diseases, and also of atherosclerosis. Leukocytes emigrate from the blood into inflamed tissues through a series of adhesion events ("the adhesion cascade"), each of which is dependent upon the state of endothelial cell activation. Initial rolling of neutrophils on vascular endothelium is mediated by transient interactions between selectins (L-selectin on leukocytes, E-selectin on cytokine-activated endothelial cells (EC) and P-selectin on both activated EC and activated platelets) and carbohydrate-bearing counter-structures on the opposing cell. Whilst rolling, leukocytes become exposed to activating signals (such as chemokines), resulting in an upregulation of the capacity of b2 integrins (eg LFA-1, Mac-1) to bind ligands (eg ICAM-1, -2) on EC. This integrin-mediated secondary adhesion results in leukocyte arrest and is followed by their transmigration into the tissues. In the case of mononuclear cells, adhesion of a4 ...
Statins Nonlipid Effects on Vascular Endothelium through eNOS Activation Curator, Author,Writer, Reporter: Larry Bernstein, MD, FACP Categories of Research: Disease biology, Cell Biology and Cell Signaling, Biological Networks and Gene Regulation, Pharmacotherapy of Cardiovascular Disease, Nitric Oxide, HMG Co A inhibitors, Endothelial Receptor, Hypertension, Therapeutic Targets Introduction Statins have an effect on the…
HIV infected patients treated with abacavir might have a higher risk for the occurrence of cardiovascular events. At time of writing of this protocol the underlying mechanism is not yet elucidated, however some studies find impaired endothelial function and elevated markers of chronic inflammation in these patients,suggesting a higher lever of chronic inflammation. Recently maraviroc (Celsentri®), a CCR5-receptor antagonist, became available for treatment of patients infected with HIV-1.. Improvement of endothelial function may be a potential beneficial side effect of treatment with maraviroc, due to the potential reduction of immune activation and chronic inflammation as a result of blocking the CCR5-coreceptor. Moreover, treatment intensification of HAART with maraviroc in patients with suppressed plasma HIV_RNA may decrease plasma HIVRNA below the cut-off of 50 copies/ml as well.. The investigators hypothesize that maraviroc intensification therapy in patients on an abacavir-containing ...
Ferrara and Henzel (1989) determined that purified bovine Vegf was mitogenic to adrenal cortex-derived capillary endothelial cells and to several other vascular endothelial cells, but it was not mitogenic toward nonendothelial cells. Leung et al. (1989) demonstrated that culture media conditioned by human embryonic kidney cells expressing either bovine or human VEGF cDNA promoted proliferation of capillary endothelial cells. VEGF, a homodimeric glycoprotein of relative molecular mass 45,000, is the only mitogen that specifically acts on endothelial cells. It may be a major regulator of tumor angiogenesis in vivo. Millauer et al. (1994) observed in mouse that its expression was upregulated by hypoxia and that its cell surface receptor, Flk1 (KDR; 191306), is exclusively expressed in endothelial cells. Folkman (1995) noted the importance of VEGF and its receptor system in tumor growth and suggested that intervention in this system may provide promising approaches to cancer therapy. VEGF and ...
Ferrara and Henzel (1989) determined that purified bovine Vegf was mitogenic to adrenal cortex-derived capillary endothelial cells and to several other vascular endothelial cells, but it was not mitogenic toward nonendothelial cells. Leung et al. (1989) demonstrated that culture media conditioned by human embryonic kidney cells expressing either bovine or human VEGF cDNA promoted proliferation of capillary endothelial cells. VEGF, a homodimeric glycoprotein of relative molecular mass 45,000, is the only mitogen that specifically acts on endothelial cells. It may be a major regulator of tumor angiogenesis in vivo. Millauer et al. (1994) observed in mouse that its expression was upregulated by hypoxia and that its cell surface receptor, Flk1 (KDR; 191306), is exclusively expressed in endothelial cells. Folkman (1995) noted the importance of VEGF and its receptor system in tumor growth and suggested that intervention in this system may provide promising approaches to cancer therapy. VEGF and ...
Mechanical forces have long been known to be potent regulators of vascular endothelial function.3 Endothelial cells have evolved sophisticated sensory and regulatory ability to maintain vascular homeostasis through adaptive remodeling.20 This study addresses the question of how endothelial cells respond to mechanical strain to control the growth of the underlying VSMCs. Previously, it was known that endothelial cells can regulate VSMC proliferation.21 In particular, heparin and endothelial cell HSPGs are potent inhibitors of VSMC proliferation and FGF-2 induced mitogenesis.13,22-24 This regulation is growth state dependent, with subconfluent cultures of endothelial cells stimulating VSMC growth and postconfluent cultures inhibiting VSMC growth.12,25-28 Similarly, perlecan and endothelial-derived HSPGs have been shown to be essential in inhibiting the neointimal response to vascular injury.14,29-31 Our study adds a new dimension to these results, demonstrating that the regulation of perlecan by ...
4610 Tumor endothelial marker 7 (TEM-7) mRNA has been previously shown to be elevated in human colorectal cancer endothelium compared to normal adjacent colorectal endothelium (St. Croix et al., Science, 2000), and is a possible therapeutic target for antiangiogenic intervention in colorectal cancer.. We evaluated TEM-7 mRNA expression in human microvascular endothelial cells (HMVEC), human umbilical vein endothelial cells (HUVEC) and endothelial precursor cells (EPC). We found that TEM-7 was not expressed in either HMVEC or HUVEC but was present in EPC. We stimulated HMVEC, HUVEC and EPC with 100 nM of the phorbol ester PMA and found that TEM-7 mRNA was induced by PMA in EPC but not in HMVEC or HUVEC. Given that EPC are closer, at the molecular level, to tumor endothelium than they are to normal quiescent endothelium (Bagley et al., Cancer Research, 2003) and that PMA is a potent transcriptional activator of cancer-associated genes, the induction of TEM-7 by PMA in EPC suggests that TEM-7 may ...
Hematogenous metastasis requires the arrest and extravasation of blood-borne tumor cells, possibly involving direct adhesive interactions with vascular endothelium. Cytokine activation of cultured human endothelium increases adhesion of melanoma and carcinoma cell lines. An inducible 110-kD endothelial cell surface glycoprotein, designated INCAM-110, appears to mediate adhesion of melanoma cells. In addition, an inducible endothelial receptor for neutrophils, ELAM-1, supports the adhesion of a human colon carcinoma cell line. Thus, activation of vascular endothelium in vivo that results in increased expression of INCAM-110 and ELAM-1 may promote tumor cell adhesion and affect the incidence and distribution of metastases.. ...
The recruitment of leukocytes to sites of infection and their migration through the endothelium are critical to immune responses. Transendothelial migration is essential for leukocytes to respond to foreign microorganisms, but if uncontrolled, can cause autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis. In order to evaluate the transmigration of leukocytes, we have developed a kinetic, label-free in vitro assay to automatically acquire and analyze transendothelial migration, with the added ability to monitor monolayer integrity.. Using primary T cells and Human Umbilical Vein Endothelial cells (HUVEC), we evaluated the ability of this novel assay to quantify leukocyte transmigration in the absence of cell labeling. Briefly, endothelial cells were grown to confluence on a physiological surface. Leukocytes were added to the monolayer, and the upper chamber was placed into a reservoir plate containing chemoattractant. Live cell images were captured at regular ...
The ability of lysoPC, either independently or as a component of oxidized LDL, to inhibit endothelial-dependent vasorelaxation is well established (Cowan and Steffen, 1995; Freeman et al., 1996). The effect of lysoPC to impair endothelium-dependent relaxation is generalized to a variety of endothelium-dependent vasodilators, including acetylcholine (Kugiyama et al., 1990), 5-hyroxytryptamine (Cox and Cohen, 1996a), thrombin (Murohara et al., 1994) and calcium ionophore A23187 (Mangin et al., 1993). However, the cellular pathways affected by lysoPC that ultimately result in endothelial vasomotor dysfunction remain unclear. LysoPC was recently documented to stimulate PLD activity in cultured human endothelial cells (Cox and Cohen, 1996c), although the role of this effect in the vasomotor actions of lysoPC was not addressed. The present study has demonstrated the ability of lysoPC to stimulate vascular PLD activity in isolated blood vessels and has documented a close association between the ability ...
TY - JOUR. T1 - Endothelial cells regulate cardiac contractility. AU - Ramaciotti, Claudio. AU - Sharkey, Angela. AU - McClellan, George. AU - Winegrad, Saul. PY - 1992. Y1 - 1992. N2 - Endothelial cells lining the lumen of blood vessels contain the receptors for many substances that alter the contractile tone of smooth muscle in the walls of the blood vessels. In response to their interaction with the signal substances, the endothelial cells release vasoactive factors that modify the contractile state of the vascular smooth muscle. This study was conducted to determine if endothelial cells can also modulate the contraction of cardiac muscle cells and contribute to the physiological regulation of the heart. The venous effluent from the coronary circulation of an isolated perfused working heart was reoxygenated and used to superfuse a trabecula isolated from the right ventricle of another heart. The peak tension and the duration of the contraction of the trabecula were reversibly altered by the ...
Objective: Peroxisome proliferator-activated receptor γ (PPARγ) agonists reduce blood pressure (BP) and vascular injury in hypertensive rodents and humans. Pparγ inactivation in vascular smooth muscle cells (VSMC)using a tamoxifen inducible Cre-Lox system enhanced angiotensin II-induced vascular injury. Transgenic mice overexpressing endothelin (ET)-1selectively in the endothelium (eET-1) exhibit endothelial dysfunction, increased oxidative stress and inflammation. We hypothesized that inactivation of Pparγ in VSMC(smPparγ-/-)will exaggerate ET-1-induced vascular damage.. Methods and Results: Elevenweek-old male control, eET-1, smPparγ-/-and eET-1/smPparγ-/- mice weretreated with tamoxifen (1 mg/kg/day, s.c.) for 5 days and sacrificed 4 weeks later. Systolic BP was higher in eET-1compared to control (123±5 vs 109±2 mmHg,P,0.05)and unaffected by Pparγ inactivation.Mesenteric artery (MA) vasodilatory responses to acetylcholine were impaired only in smPparγ-/- (P,0.05) compared to ...
This paper addresses the hypothesis that the expression of members of the NDST enzyme family can vary between different cell types and following stimulation by pro-inflammatory cytokines. The immortalized human microvascular endothelial cell line HMEC-1 was used to model the effect of cytokine-mediated regulation of NDST expression on the abundance of sulphated domains within HS on the surface of the vascular endothelium. This was followed by an examination of changes in the potential of these cells to bind exogenous RANTES at their apical surface and subsequent analysis of changes in the biological activity of this chemokine. The HMEC-1 cell line was chosen for this work as it provides a reproducible system which has previously been validated to model aspects of the immunobiology of microvascular endothelium including the uniform response to pro-inflammatory cytokines (Goebeler et al., 1997) and the presentation of antigens to specific T cells (Bosse et al., 1993). In addition, HMEC-1 cells are ...