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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial dysfunction is an early and persistent vascular abnormality in the evolution of atherothrombotic disease. Risk factors for atherosclerosis promote an inflammatory oxidative environment in the vasculature that induces pathologic changes in endothelial function, including the support of enhanced smooth muscle tone, thrombosis, and smooth muscle proliferation. This article provides an overview of the molecular basis of endothelial dysfunction and of its diagnosis and treatment.
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PMID:Roles of endothelial dysfunction in coronary artery disease. 1119 23

Coronary artery disease (CAD) is associated more closely with atherosclerosis in the popliteal than in the brachial artery. This case-control study aimed at clarifying whether endothelial dysfunction of patients with CAD can be detected non-invasively in the popliteal artery by means of ischemia-induced flow-mediated dilation (FMD) and cold pressor reaction (CPR), and how it compares with the brachial artery. We further investigated a new mode of evaluation of the CPR. Eleven cases with CAD were compared with 16 matched healthy controls. Popliteal and brachial arterial diameter was monitored by ultrasound for 20 min following ischemia and cold pressor. For CPR, the difference between maximum and minimum diameter was defined as maximum vasomotion. In the popliteal artery, maximum vasomotion and FMD were significantly smaller in cases than in controls, the difference being more pronounced than in the brachial artery, where only maximum vasomotion was significantly smaller. After exclusion of current smokers, only the difference in maximum vasomotion of both arteries remained significant. We conclude that maximum vasomotion may be more sensitive for detection of endothelial dysfunction than FMD. Endothelial dysfunction in patients with CAD is more pronounced in the popliteal artery than in the brachial artery.
Atherosclerosis 2001 Mar
PMID:Endothelial function of the popliteal artery in patients with coronary artery disease. 1122 41

Endothelial dysfunction plays a major role in the pathogenesis of atherosclerosis. Pro-inflammatory cytokines such as interleukin-1 beta and tumour necrosis factor alpha activate endothelial cells changing their resting phenotype to become pro-adhesive, pro-thrombotic and pro-atherogenic. Phage display in vivo biopanning has been used to identify peptide sequences that home to diseased regions of the vessel wall in low density lipoprotein receptor (LDLr) knockout mice. In LDLr knockout mice, peptide sequence determinants exhibiting organ specificity have been isolated. These sequences have applications for gene delivery, drug delivery and for improving contrast agents for vascular imaging.
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PMID:Homing markers for atherosclerosis: applications for drug delivery, gene delivery and vascular imaging. 1124 40

Endothelial dysfunction has been shown in a wide range of vascular disorders including atherosclerosis and related diseases. Here, we examine and address the complex relationship among nitric oxide (NO)-mediated pathways and atherogenesis. In view of the numerous pathophysiological actions of NO, abnormalities could potentially occur at many sites: (a) impairment of membrane receptors in the arterial wall that interact with agonists or physiological stimuli capable of generating NO; (b) reduced concentrations or impaired utilization of l-arginine; (c) reduction in concentration or activity both of inducible and endothelial NO synthase; (d) impaired release of NO from the atherosclerotic damaged endothelium; (e) impaired NO diffusion from endothelium to vascular smooth muscle cells followed by decreased sensitivity to its vasodilator action; (f) local enhanced degradation of NO by increased generation of free radicals and/or oxidation-sensitive mechanisms; and (g) impaired interaction of NO with guanylate cyclase and consequent limitation of cyclic GMP production. Therefore, one target for new drugs should be the preservation or restoration of NO-mediated signaling pathways in arteries. Such novel therapeutic strategies may include administration of l-arginine/antioxidants and gene-transfer approaches.
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PMID:Nitric oxide and atherosclerosis. 1129 58

Endothelial dysfunction, believed to underlie the structural changes of atherosclerosis, is a systemic phenomenon. Despite this, the radial artery has been considered as devoid of atherosclerosis and is commonly used as a conduit in coronary artery bypass grafting (CABG). Recently, histological study has shown intimal hyperplasia and other structural changes consistent with early atherosclerosis in the radial artery. The objective of the present study was to determine if structural changes in the radial artery could be detected in vivo in patients with coronary atherosclerosis. Using high resolution echo-tracking, measurements of radial artery internal diameter, wall thickness and wall cross-sectional area were made in 25 patients awaiting CABG and in 20 controls. Digital and brachial blood pressures were also recorded. Mean arterial pressures did not differ between the patient and control groups. All measures of wall thickness were greater in the patient than the control group. Neither current arterial pressures nor past history of hypertension correlated with wall thickness. Using a model of analysis of covariance, coronary artery disease was the best single predictor of intima-media thickness, R(2)=48%, n=44, P<0.0005. We concluded that increased radial artery wall thickness can be demonstrated in vivo in patients with coronary atherosclerosis. This is a novel observation which seems to be independent of blood pressure, and is consistent both with the hypothesis of systemic endothelial dysfunction leading to systemic structural changes and also to the recent histological evidence for atherosclerotic changes in this vessel.
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PMID:Radial artery hypertrophy occurs in coronary atherosclerosis and is independent of blood pressure. 1129 91

Endothelial dysfunction can be detected in the early phase of atherosclerosis. Two unresolved questions have been raised the wether, (1) the dyslipidemic state alone without any other risk factors can be harmful for the endothelial function measured by ultrasound, and (2) the use of the antilipidemic fibrate is sufficient to influence the endothelial functions. From 38 subjects with solitary combined dyslipidaemia 32 (84%) showed endothelial dysfunction measured by flow mediated vasodilatation (FMD) on the forearm and this group of patients was featured only by higher fibrinogen levels (no differences on BMI, serum lipid and glucose level). The patients with endothelial dysfunction were treated with 100 mg of ciprofibrate per day (12 women, 20 men, average age: 44.6 +/- 9 years, BMI 24.6 +/- 3.4 kg/m2). The pretreatment serum lipid levels were: total cholesterol 6.9 +/- 0.4, triglyceride 4.2 +/- 0.3, HDL cholesterol 1.13 +/- 0.21 mmol/l. After the 4 weeks treatment period the cholesterol and triglyceride level decreased, the concentration of HDL cholesterol increased significantly, which changes were in correspondence with significant improvement of FMD (3.9 +/- 0.7% vs. 7.0 +/- 1.6%). The level of fibrinogen also declined significantly. At the 8th week there were no significant further changes compared to the data received at the 4th week. Using the lineal regressive analysis the improved vasodilatator respond at both check points was correlated only with the fall of total cholesterol level. The ciprofibrate was suspended after the 8th week for a 4 weeks period and the triglyceride and the fibrinogen levels increased whereas the HDL cholesterol level decreased significantly. The FMD impaired significantly (to 5.8 +/- 1.2%). There were no correlations among the changes. The results demonstrated the lipid and probably non-lipid-factors are important in these early damages of endothelial functions.
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PMID:[Effect of ciprofibrate on the endothelial dysfunction of patients with combined dyslipidemia]. 1136 62

Endothelial dysfunction is an early event in atherosclerosis and could be considered a response to the injury induced by major risk factors. There is evidence that endothelial dysfunction is intimately involved in the onset and the progression of cardiovascular disease through abnormalities in the production, release or degradation of endothelium-derived factors, mainly nitric oxide and endothelin 1. Several reports have shown that drugs of the statin class could have multiple beneficial effects related to endothelium-mediated vasoactive, antithrombotic, antiproliferative and anti-inflammatory actions. Thus, the question arises of whether endothelial cells are the main target of statin therapy, in the setting of both hypercholesterolemia and normocholesterolemia. Experimental and clinical studies are reported that could support this hypothesis.
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PMID:HMG-CoA reductase inhibitors: Is the endothelium the main target? 1138 85

Endothelial cells play diverse biological roles, such as maintaining vascular tone and structure. Recent progress in vascular biology has revealed that the endothelium releases a large number of vasoactive substances. These substances are divided into two classes: endothelium-derived relaxing factors(EDRFs), and endothelium-derived contracting factors(EDCFs). It has been shown that EDRFs such as nitric oxide(NO) protects vasculature from atherogenic insults, whereas EDCFs, such as endothelin, have opposite effects and participate in the progression of cardiovascular diseases. The exposure of coronary risk factors decreases the bioactivity of EDRFs and increases the release of EDCFs. Endothelial dysfunction caused by imbalance between EDRFs and EDCFs precedes and promotes atherosclerosis by several mechanisms, such as adhesion of monocytes and platelets, increase in vascular permeability, proliferation and migration of smooth muscle cells. In this article, physiology and pathophysiology of these endothelium-derived substances will be reviewed.
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PMID:[Recent trends in studies of the etiology of hypertension: Endothelium-derived factors]. 1139 86

Endothelial dysfunction is generally believed to be the inciting event in atherosclerosis, and is probably important in ischemic manifestations as well. The release of endothelium-derived vasoactive substances is not only triggered by acetylcholine, but also controlled by a host of neuromediators and by shear forces exerted by the blood flowing through the blood vessel. However, this balance is altered in disease states such as atherosclerosis, diabetes, chronic heart failure, coronary artery disease, or hypertension. The most important mechanism in the decrease in endothelium-dependent relaxation appears to be a reduced release of nitric oxide. In healthy people, the predominant effect of stimulation of the endothelium is vasodilation. It is tempting to hypothesize that endothelial dysfunction is one of the initial steps involved in the development of atherosclerosis, but also in peripheral artery atherosclerosis. Impairment of endothelium-dependent vasodilation in the coronary arteries has been demonstrated not only in patients with documented atherosclerosis and/or established cardiovascular risk factors. Noninvasive evaluation of brachial artery vasoactivity using high resolution B-mode ultrasound is currently being established to evaluate endothelial function. We studied the endothelial function in 50 normal volunteers, 28 hypertensive subjects, and 31 hypercholesterolemia subjects. The diameter of the target artery was measured from two-dimensional ultrasound images with 10 MHz linear transducer. The results suggested that antihypertensive therapy with a certain calcium antagonist did not have a favorable effect on endothelial function and after cessation of cholesterol lowering therapy, the endothelial dysfunction developed again. The endothelial function can now be readily measured in humans and is very useful research tool to assess the effect of risk factors and their treatment on vascular function. Endothelial function testing will assume a prominent role in the evaluation and treatment of patients at risk of developing coronary atherosclerosis and its sequelae.
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PMID:Noninvasive evaluation of endothelial function. 1143 34

Endothelial dysfunction plays a pivotal role in the initial stage of atherosclerosis. Insulin resistance is associated with accelerated atherosclerosis, especially coronary heart disease. To elucidate the relationship between endothelial dysfunction and insulin resistance or insulin resistance syndrome in patients with type 2 diabetes, we investigated the correlation between plasma soluble thrombomodulin (TM) and von Willebrand factor (vWF), measures of endothelial dysfunction, and the degree of insulin resistance evaluated by homeostasis assessment models of insulin resistance (HOMA-IR), or variables of insulin resistance syndrome. We studied 53 patients with type 2 diabetes, 23 treated with diet alone and 30 treated with sulfonylureas, who had normal renal function. The plasma soluble TM concentrations were highly correlated with HOMA-IR (r=0.64, p<0.0001), the plasma insulin (r=0.72, p<0.0001), the systolic blood pressure (r=0.45, p=0.0005), and the plasma fibrinogen (r=0.43, p=0.0018), while they were inversely correlated with the serum HDL cholesterol concentrations (r=-0.27, p=0.0344). The plasma vWF concentrations were positively correlated with HOMA-IR (r=0.35, p=0.0151) and the plasma fibrinogen (r=0.32, p=0.0203), but not with the plasma insulin, the systolic blood pressure or the HDL cholesterol concentrations. Furthermore, plasma TM, but not vWF, was positively correlated with total number of variables of insulin resistance syndrome (r=0.45, p=0.0005). These results indicate that endothelial dysfunction may be associated with the pathogenesis of insulin resistance syndrome as well as insulin resistance, and that the plasma TM might reflect endothelial damage better than the plasma vWF in the state of insulin resistance in patients with type 2 diabetes.
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PMID:Relationship between plasma soluble thrombomodulin levels and insulin resistance syndrome in type 2 diabetes: a comparison with von Willebrand factor. 1145 33


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