Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis is characterized by hypertrophy of the vascular media, intimal thickening and lipid-containing plaques. Atherosclerosis is a progressive systemic vascular disease which leads to impaired tissue perfusion due to vascular obstruction. In advanced stages it is often complicated by thrombosis. Recent research demonstrates that atherosclerosis is also a functional disease. In atherosclerosis and hypercholesterolemia, normal vasodilatation is impaired due to endothelial dysfunction. In addition, the ability of the vessel wall to reject adhering and aggregating platelets is deteriorated. Endothelial dysfunction in atherosclerosis is characterized by impaired formation of nitric oxide (NO), formerly known as endothelium-derived relaxing factor (EDRF). NO is continuously formed in the vascular endothelium and promotes tissue perfusion by relaxation of vascular smooth muscle. Endogenously formed NO may also protect against foam cell formation and media hypertrophy, i.e. against the structural component of atherosclerosis. In patients with ischaemic heart disease, the endothelial dysfunction leads to decreased ability to dilate the coronary vessels in response to several forms of physiological stimuli. Endothelial dysfunction in atherosclerosis is reversed by lipid-lowering therapeutic interventions.
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PMID:Nitric oxide (NO) in the cardiovascular system: role in atherosclerosis and hypercholesterolemia. 786 90

The intercellular adhesion of circulating leukocytes to vascular endothelium is a prerequisite for leukocyte emigration from the blood to extravascular tissues. This process is facilitated by adhesion molecules on the surfaces of both the vascular endothelial cells and the leukocytes. The experiments presented here demonstrate for the first time that the leukocyte adhesion receptor, intercellular adhesion molecule-1, is constitutively expressed on cultured cerebromicrovascular endothelial cell lines derived from both spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats. Both cultures contained similar numbers of cells constitutively expressing this adhesion molecule (31.4% and 29.6%, respectively). Adhesion molecule expression was up-regulated by interleukin-1 beta, tumor necrosis factor-alpha, interferon-gamma and lipopolysaccharide in a dose- and time-dependent manner. Both cultures exhibited similar maximum levels of adhesion molecule up-regulation to optimal concentrations of all three cytokines. However, SHR endothelial cells were more sensitive to all three cytokines; significantly higher levels of intercellular adhesion molecule-1 expression were seen on SHR as opposed to WKY endothelial cells cultured with sub-optimal cytokine concentrations. It was also observed that lipopolysaccharide up-regulated intercellular adhesion molecule-1 expression on SHR endothelial cells to a greater extent than on WKY endothelial cells. The findings that intercellular adhesion molecule-1 can be up-regulated to a greater degree on SHR endothelial cells may have important implications for in vivo perivascular leukocyte accumulation under hypertensive conditions. These observations indicate a possible mechanism by which hypertension may predispose to the development of disorders such as atherosclerosis and stroke.
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PMID:Adhesion molecules on normotensive and hypertensive rat brain endothelial cells. 790 12

Our appreciation of the vascular endothelium has changed considerably over the last decade. This organ, finally recognized as such, participates actively in vasomotor regulation and haemostasis. It secretes several relaxing and contracting factors which act locally to determine resting vascular tone. One of the relaxing factors, EDRF/NO plays an important physiological role as it contributes to the rapid adaptation of blood flow to various pharmacological and mechanical stimuli, thereby ensuring maintenance of adequate tissue perfusion. Nitric oxide (NO) is an ubiquitous factor which was crowned "molecule of the year 1992" by the scientific review Science. Its effects extend well beyond those on the cardiovascular system. Endothelial dysfunction is observed in many pathological states such as atherosclerosis, reperfusion injury, postangioplasty endothelial regeneration, degeneration of venous bypass grafts, pure spastic angina, hypertension and diabetes. It is associated with decreased production of EDRF/NO, which probably contributes significantly to the aggravation of endothelial and parietal lesions and to the natural progression of atherosclerotic disease in general. This article describes the principal vasoactive factors secreted by the endothelium and goes on to list the physiologic cardiovascular effects of EDRF/NO in detail, and to review the different pathologies associated with a disorder of secretion of this factor.
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PMID:[EDRF/NO and endothelial functions]. 801 Aug 61

The vascular endothelium that forms an interface between the blood and the surrounding tissues is continuously exposed to both physiologic and pathophysiologic stimuli. These stimuli are often mediated by nutrients that can contribute to the overall function of the endothelial cell in the regulation of vascular tone, coagulation and fibrinolysis, cellular growth and differentiation, and immune and inflammatory responses. Therefore, nutrient-mediated functional changes of the endothelium and the underlying tissues may be significantly involved in the atherosclerotic disease process. There is evidence that individual nutrients or nutrient derivatives may either provoke or prevent metabolic and physiologic perturbations of the vascular endothelium. Preservation of nutrients that exhibit antiatherogenic properties may, therefore, be a critical issue in the preparation and processing of foods. This review focuses on selected nutrients as they affect endothelial cell metabolism and their possible implications in atherosclerosis.
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PMID:Nutrition, endothelial cell metabolism, and atherosclerosis. 806

Impairment of the vascular endothelium and its functions is a common sign of several serious diseases (atherosclerosis, hypertension, vascular spasms, thromboses) and is the initial stage of vascular affection in diabetes mellitus. The endothelium plays an important role in the transformation of some substances with a cardiovascular action and it secretes itself vasoactive substances. Vascular affections in diabetes are characterized by impaired homeostasis of vasoactive substances of endothelial origin--raised levels of vasoconstrictor factors (endothelins, thromboxanes) and reduction of vasodilatating factors (prostacyclin, EDRF--endothelin derived relaxing factor) as well as disorders of their interrelations. Vasoactive agents lead at the same time also to alteration of the growth and proliferation potential of smooth muscle cells of the vascular wall and thus to remodelling of the vascular structure in diabetes. At present possible ways how to influence these processes in a favourable way are intensely studied and discussed.
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PMID:[Endothelial dysfunction in diabetes mellitus]. 806 97

The vascular endothelium plays an active role in physiological processes such as hemostasis, regulation of vessel tone and vascular permeability. Cell injury, or any event which disrupts endothelial integrity and thus endothelial permeability properties, may be involved in the early events leading to atherosclerotic lesion formation. Because of its constant exposure to blood components, including prooxidants, diet-derived fats and their derivatives, the endothelium is susceptible to oxidative stress and to injury mediated by blood lipid components. It is likely that these events potentiate the overall inflammatory response to injury by increasing cytokine release in proximity to the endothelium, which then could further disrupt endothelial barrier function. Even though mechanisms associated with lipid/cytokine-mediated endothelial cell dysfunction are unclear, our data suggest that they may be both oxidative and non-oxidative in nature. We suggest that dietary fats, rich in certain unsaturated fatty acids are atherogenic by enhancing the formation of reactive oxygen intermediates. These intermediates can activate oxidative stress-responsive transcription factors, such as NF-kappa B, which in turn may promote cytokine production, adhesion molecule expression and ultimately endothelial barrier dysfunction. The resulting disturbances in endothelial integrity possibly allow increased penetration of cholesterol-rich lipoprotein remnants into the arterial wall, a critical event in the etiology of atherosclerosis. Data suggest that certain nutrients, which have antioxidant and/or membrane stabilizing properties, protect endothelial cells by interfering with the above proposed mechanisms of endothelial cell dysfunction.
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PMID:Influence of nutrients and cytokines on endothelial cell metabolism. 807 69

Several recent postmortem studies suggest an increased prevalence of atherosclerosis in young habitual cocaine abusers. However, little is known about the effects of cocaine abuse on the vascular endothelium and its relationship to atherosclerosis. Therefore, the consequence of chronic administration of intravenous cocaine on the induction of aortic sudanophilia was examined. Male New Zealand White rabbits were fed a 0.5% cholesterol diet for 10 wk. During this period, animals were randomized to receive either cocaine-hydrochloride (0.25 mg/kg) intravenously (n = 17) twice daily; or an equivalent volume of 0.9% physiologic saline, control group (n = 16). Mean values for total circulating leukocytes and platelets and total plasma cholesterol and triglycerides were similar in both groups throughout the protocol. At the completion of the study, aortic sudanophilia was measured and expressed as a percentage of regional involvement (R1 = proximal 4 cm, R2 = middle 6 cm, and R3 = distal 10 cm). Statistical significance among groups was achieved in the proximal thoracic aorta (p = 0.057). No significant differences in sudanophilia were noted in the middle and distal segments. When animals were placed in subgroups according to percent total plaque involvement, there was a significant increased distribution of rabbits with a greater extent of sudanophilia in the cocaine-treated group as compared with control (p = 0.01, chi-square analysis). Immunocytochemical studies using the macrophage-specific and muscle actin-specific monoclonal antibodies demonstrated that sudanophilic areas in both groups were predominantly composed of macrophage-derived foam cells. Evaluation of plaque morphology showed an increase in intimal plaque thickness and in the number of macrophages and smooth muscle cells in cocaine-treated animals; however, group differences were not statistically significant. Because no significant differences were found in the cellular composition of atherosclerotic plaques between groups, further studies were performed to assess the effects of cocaine on the permeability function of cultured endothelial cell monolayers as a possible mechanism of increased sudanophilia. Cocaine (100 microM)-treated endothelial cell monolayers demonstrated an increased permeability to horseradish peroxidase during all time intervals studied (0-6 hr). Permeability differences were statistically significant at 30 min and 1 hr (p = 0.003 and 0.02, respectively). Collectively, these observations suggest that administration of cocaine to cholesterol-fed rabbits increases the prevalence of aortic sudanophilia via at least one possible mechanism involving enhanced vascular permeability.
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PMID:Increased prevalence of aortic fatty streaks in cholesterol-fed rabbits administered intravenous cocaine: the role of vascular endothelium. 811 19

The vascular endothelium plays a vital role in the control of the circulation. It metabolizes various vasoactive substances, coverts angiotensin I to angiotensin II and secretes the potent vasodilators prostacyclin and EDRF (NO) and the vasoconstrictor peptide endothelin-1. The balance between these mediators determines the responses of the cardiovascular system in diseases such as hypertension, atherosclerosis and myocardial infarction.
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PMID:The Croonian Lecture, 1993. The endothelium: maestro of the blood circulation. 814 36

The vascular endothelium is the site of formation of several powerful mediators. One of these is NO, a chemically unstable radical formed by enzymatic conversion of L-arginine in the presence of molecular oxygen. NO elicits relaxation of VSMC by activating cytosolic guanylate cyclase. NO also counteracts platelet adhesion and aggregation. The biological actions of NO make it a key substance in the endogenous defense against vascular occlusion and thrombosis. The basal formation of NO maintains a moderate but significant vasodilation in the systemic resistance vessels and counteracts platelet activity. When blood flow in conduit arteries is increased there is an augmented endothelial formation of NO, eliciting flow-dependent vasodilation. Beside this, several vasodilators (acetylcholine, bradykinin, histamine, substance P) operate by stimulating endothelial NO formation. On the other hand, drugs like nitroglycerin and papaverine operate independently of the vascular endothelium. Vasodilator mechanisms, physiological as well as pharmacological, may therefore be characterized as endothelium-dependent (i.e. NO-mediated), or endothelium-independent (i.e. not mediated by NO). Physiologically, mixed mechanisms occur. Failure of the vascular endothelium to elicit NO-mediated vasodilatation may be due to decreased formation, increased degradation, decreased sensitivity to the NO formed, or a mixture of these factors. Irrespective of the mechanism behind, this is referred to as endothelial dysfunction. Endothelial dysfunction occurs in several cardiovascular settings, like atherosclerosis, hypercholesterolaemia, diabetes, and essential hypertension. Endothelial dysfunction leads to an impaired tissue perfusion, increased local vascular resistance, decreased defense against thrombus formation, and possibly also decreased defense against hypertrophy of the VSMC in the vessel wall media. In patients with CHD, endothelial dysfunction leads to an impaired coronary flow response to physical and mental stress, and to promotion of platelet adherence and aggregability. Endothelial dysfunction is thereby a probable aggravating factor in the atherosclerotic process, adding a functional component on top of the structural lesions characterizing this disease. A particular form of endothelial dysfunction, limited to the arterial resistance vessels, may explain the symptoms and clinical characteristics of microvascular angina. In patients with essential hypertension, endothelial dysfunction prevails, adding a functional component to the structural factors also in this disease. Hitherto, the only therapeutic tools available to restore endothelial dysfunction appear to be restriction of the dietary intake of lipids, possibly reinforced with intake of antioxidants like fish oil and vitamin E. However, large clinical trials to confirm the efficacy of such therapy in reversing endothelial dysfunction have not been conducted. In the future, more directly acting therapeutic regimens, aimed at supporting or substituting the endogenous formation of NO, are likely to appear as well.
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PMID:Endothelial nitric oxide and cardiovascular disease. 815 Dec 63

Modulation of vascular tone is one important function of the endothelium. This can occur via two principal mechanisms: by modulating the local concentration of circulating vasoactive substances (e.g. adenine nucleotides, angiotensin II, biogenic amines, bradykinin), and by synthesizing and releasing vasoactive autacoids. The most important endothelium-derived vasodilator autacoids are nitric oxide (NO) and prostacyclin (PGI2). By counteracting neuro- and myogenic vasoconstriction, the continuous release of these autacoids from the vascular endothelium represents a sensitive and highly effective local system for maintaining an adequate blood flow to the organs. Impaired production of NO (and PGI2), either as a result of endothelial injury or dysfunction, has been implicated in the pathology of a variety of cardiovascular diseases, such as hypertension, hypercholesterolaemia, atherosclerosis and diabetes. Therefore, the prevention and/or reversal of the functional and morphological changes of the endothelium associated with these diseases is an important therapeutic goal. This brief overview covers current knowledge concerning the intracellular pathways that link endothelial activation by receptor-dependent and -independent stimuli to the formation of NO and PGI2.
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PMID:Signal transduction in endothelium-dependent vasodilatation. 829 77


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