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

Elevated plasma levels of homocysteine and disulfide adducts of homocysteine (collectively termed "homocyst(e)ine") are associated with increased risk of thrombotic and atherosclerotic vascular disease. It is still not evident, however, whether moderately elevated plasma homocyst(e)ine concentration per se is a cause, or rather just a marker for an associated condition that may predispose to development of vascular disease or its complications. This distinction has important clinical consequences, since dietary intervention to lower plasma homocyst(e)ine has been proposed as a global strategy to decrease the prevalence of vascular disease. Studies of cultured cells in vitro have led to the hypothesis that homocysteine may predispose to vascular disease by altering the normally antithrombotic and vasoprotective phenotype of vascular endothelium, perhaps through a mechanism that involves generation of peroxides and other reactive oxygen species. Recent findings in animal and human models of moderate hyperhomocyst(e)inemia provide support for some aspects of this hypothesis. Endothelial dysfunction in hyperhomocyst(e)inemia may contribute to development of atherosclerosis and predispose to complications such as thrombosis and vasospasm. Important questions to be addressed in future investigations include the relative importance of homocysteine versus associated conditions (such as folate deficiency) in the etiology of vascular dysfunction, the role of homocysteine-induced oxidant stress, and the potential benefits of lowering plasma homocyst(e)ine levels through dietary supplementation with B vitamins.
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PMID:Homocysteine and vascular dysfunction. 932 62

Growth factors such as fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) exert important effects on endothelial cells in vitro and in vivo. This article reviews the effect of these two growth factors on endothelial dysfunction in various animal models of vascular disease: (1) collateral circulation supplying an ischemic territory, (2) balloon injury, and (3) diet-induced experimental atherosclerosis. Endothelial dysfunction may limit the beneficial effects of collateral vessels on tissue perfusion. Administration of VEGF or basic FGF (bFGF) augments collateral development in different models of hindlimb ischemia by enhancing neovascularity and by facilitating the recovery of endothelial function in the collateral circulation. Similarly, studies performed after balloon angioplasty have demonstrated abnormal responses of previously dilated sites to endothelium-dependent agonists. Administration of VEGF or bFGF increases endothelial regrowth and normalizes endothelium-dependent responses after experimental angioplasty. Finally, endothelium-dependent relaxation is impaired in diet-induced experimental atherosclerosis. It was recently demonstrated that hypercholesterolemic rabbits treated with bFGF had significantly better endothelium-dependent responses than those not treated with bFGF. These results show that in vivo administration of the endothelial cell growth factors VEGF and bFGF leads to significant improvement in endothelium-dependent responses and supports the concept of using these growth factors as a new therapeutic strategy for patients with vascular diseases.
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PMID:Growth factors as a potential new treatment for ischemic heart disease. 942 53

Endothelial dysfunction is considered a key early event in atherosclerosis. Using a novel ultrasound method, brachial artery endothelial and smooth muscle physiology were studied in 20 adolescents with IDDM and compared to that in 20 nondiabetic subjects matched for age (13-22 years), gender and vessel size. Endothelium-dependent dilatation (EDD) was assessed in response to flow (EDD) and endothelium-independent vasodilatation after sublingual glyceryl trinitrate (GTN). Both EDD and GTN were reduced in those with IDDM compared with controls: 5% vs 9%, (p = 0.0002) and 14% vs 21% (p = 0.002). Abnormal EDD was found in 12 IDDM adolescents (diabetes duration 3.3-14.9 years). The maximum albumin excretion rate of the diabetic group was 17 micrograms/min. Four adolescents had retinopathy assessed by stereoscopic fundus photography. Three had at least one of four cardiovascular autonomic test abnormalities. There was no significant correlation observed between the test for early large vessel disease and those for diabetic microangiopathy. Large vessel dysfunction was the most common abnormality.
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PMID:Large vessel dysfunction in diabetic adolescents and its relationship to small vessel complications. 946 29

There are three findings suggesting the inflammatory and immunogenic nature of the atherosclerosis: Firstly the colocalisation of macrophages/monocytes and T-lymphocytes in all phases of the atherosclerosis, starting with intimal damages and developing into the end stage of atheromatous plaques, secondly the production of cytokines and thirdly the expression of MHC II antigens. The persisting chlamydia pneumoniae bacteria infection, which has been repeatedly detected in the intima, sustains this inflammatory process. Endothelial dysfunction and an expression of adhesion molecules, which might have been triggered by the chlamydial infection, could lead to atherosclerotic lesions according to the "response to injury" theory. The chlamydiae specific findings can well be integrated into this concept: Two of three classical Koch postulates are nearly fulfilled. There is additional direct and indirect evidence--particularly the first positive results of oral antibiotic therapy after acute myocardial infarction--suggesting a causative role. The unfavourable changes in the lipid profile, which might be brought about by the infection, may also contribute. Repeated chlamydial reinfections trigger the immune system through the cellular memory of T-lymphocytes sustaining the intramural inflammatory process. This leads to an activation of metalloproteinases with a fissuring on the plaques and finally to thrombosis. If this suggested link is confirmed, the latent chlamydia infections could be another treatable risk factor apart from the classical cardiovascular risk factors.
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PMID:[Is arteriosclerosis an infectious disease?]. 949 88

The vascular endothelial cell is a multipotent cell which has several functions: transport barrier, phagocytosis, coagulation/anticoagulation, fibrinolysis, autocrine/paracrine and metabolic functions. The release of vasoactive agents, such as the vasodilators EDRF (NO) and EDHF, and vasoconstrictors, such as endothelin (ET), represents an important local mechanism altering the balance of vasodilation/ vasoconstriction of the vascular smooth muscle cell. Inhibition of the synthesis of NO by exogenous (e.g. L-NAME) or endogenous (e.g. ADMA) L-arginine analogues may cause transient or sustained hypertension. A similar effect may be achieved by continuous administration of the potent vasoconstrictor ET. Endothelial dysfunction, associated with a deficient NO production and release as well an enhanced ET generation, may be present in some forms of vascular disease, such as hypertension, atherosclerosis, diabetes mellitus or sleep apnea. Whether such alterations may be a cause of hypertension and involved in the maintenance of high blood pressure or whether they represent a consequence of the hypertensive disease remains to be concluded. Furthermore, while there is emerging evidence that endothelial dysfunction in cardiovascular disease may be reversed by therapy, it remains to be determined whether measures of endothelial function in man may serve as predictors for morbidity or mortality.
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PMID:Measures of endothelial function as an endpoint in hypertension? 949 29

Endothelial dysfunction is a key feature of diabetes mellitus and is thought to be the major cause of vascular complications associated with the disease. The vascular endothelium demonstrates impaired synthesis of vasodilators and increased release of procoagulants and vasoconstrictors, defects which theoretically could explain the increased incidence of atherosclerosis and hypertension found within this patient group. The pathways mediating endothelial cell layer dysfunction are unknown, although many candidates have been proposed. This review concentrates on the hypothesis that increased oxidative stress combined with abnormal plasma lipid composition leads to reduced synthesis of endothelial vasodilators and hence endothelial dysfunction. Free radical generation is undoubtedly raised in diabetes but the evidence for decreased antioxidant status is debatable. The role of antioxidant and lipid-lowering therapy is considered, but few studies have directly investigated the effect of treatment on vascular function. Concern arises from individual studies of vitamin E in diabetic animals which have proved deleterious. Current literature implies that a combination therapy of vitamin E and vitamin C may be beneficial, but this needs to be investigated further in both animal and human diabetes.
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PMID:Oxidative stress and lipids in diabetes: a role in endothelium vasodilator dysfunction? 954 38

Endothelial dysfunction is an important early event in atherogenesis. Changes in arterial endothelial physiology were studied in patients with severe primary hypercholesterolaemia participating in an ongoing clinical trial evaluating atorvastatin and simvastatin. Endothelial function was assessed non-invasively using brachial ultrasound and the primary outcome measure was flow-mediated endothelium-dependent dilatation (FMD) in response to reactive hyperaemia. Patients were studied upon entry while still using simvastatin 40 mg daily and again after a 10-week washout (baseline). Over the next 30 weeks, 20 patients received atorvastatin titrated up to 80 mg daily and 12 patients received simvastatin titrated up to 40 mg daily (plus cholestyramine 4 g daily in 10/12), followed by a final ultrasound study. During simvastatin washout, total and low density lipoprotein (LDL) cholesterol rose by a median 23-29% and 30-34%, respectively. During atorvastatin therapy, total and LDL cholesterol fell by a median of 41 and 46%, respectively, triglycerides fell by 45%, and high density lipoprotein (HDL) cholesterol rose by 10%. During simvastatin plus cholestyramine therapy, the respective median changes were - 32, - 39, - 44 and + 11%. Patients at baseline showed evidence of impaired FMD and this improved significantly on either treatment, from a median + 2.2 to + 5.5% on atorvastatin and from + 1.8 to + 4.5% on simvastatin plus cholestyramine (P < 0.01 for both treatments). Typical response in healthy subjects would be from + 8 to + 9%. FMD at baseline was correlated with HDL cholesterol (r=0.49, P < 0.01). Change in FMD was inversely correlated with baseline FMD (r=-0.54, P < 0.001). Endothelial dysfunction in primary hypercholesterolaemia was improved by treatment with atorvastatin or simvastatin plus cholestyramine and this effect may result in the prevention of future coronary events.
Atherosclerosis 1998 Mar
PMID:Effects of atorvastatin monotherapy and simvastatin plus cholestyramine on arterial endothelial function in patients with severe primary hypercholesterolaemia. 956 52

Nitric oxide (NO) is the main agent of communication between the endothelium and the smooth muscle, involved in vasodilatation. Its vasodilator action requires prior tonic contraction of smooth muscle cells, related to vasoactive agents such as catecholamines or angiotensin II-induced centripetal communications and pharmaco-mechanical coupling. In physiological conditions, NO is liberated following constitutive endothelial NO synthase activity in response to shear stress generated by the dynamics of blood on the arterial wall. Endothelial dysfunction modifying NO production is implicated in different cardiovascular diseases such as hypertension, congestive heart failure and atherosclerosis.
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PMID:[Role of endothelial nitric oxide in the regulation of arterial tone]. 961 14

Endothelial dysfunction is an early event in atherosclerosis preceding the formation of plaques. An important functional consequence of endothelial damage is reduced vasodilatory responses to a variety of pharmacological and physiological stimuli including reactive hyperaemia. Hitherto, endothelial function could only be assessed by invasive techniques, but a novel ultrasound based technique has recently been developed, which allows non-invasive evaluation of endothelial function in large systemic arteries such as the brachial artery. The technique is accurate, reproducible and able to differentiate between subjects with and without vascular dysfunction. Impaired endothelial function has been documented in young and adult individuals with various vascular risk factors including cigarette smoking, diabetes mellitus, hypercholesterolaemia, and homocystinuria. A good correlation has been found between both the presence of atherosclerotic lesions and endothelial function in the coronary arteries and the brachial artery. The method may help in identification of individuals with early vascular changes and thereby make risk factor modification possible at a very early stage of the atherosclerotic process. It may furthermore serve as a tool to monitor the impact of prevention and intervention on arterial damage.
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PMID:[Non-invasive assessment of endothelial function]. 962 4

Endothelial dysfunction associated with atherosclerosis has been attributed to alterations in the L-arginine-nitric oxide (NO)-cGMP pathway or to an excess of endothelin-1 (ET-1). The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to ameliorate endothelial function. However, the physiological basis of this observation is largely unknown. We investigated the effects of Atorvastatin and Simvastatin on the pre-proET-1 mRNA expression and ET-1 synthesis and on the endothelial NO synthase (eNOS) transcript and protein levels in bovine aortic endothelial cells. These agents inhibited pre-proET-1 mRNA expression in a concentration- and time-dependent fashion (60-70% maximum inhibition) and reduced immunoreactive ET-1 levels (25-50%). This inhibitory effect was maintained in the presence of oxidized LDL (1-50 microg/ml). No significant modification of pre-proET-1 mRNA half-life was observed. In addition, mevalonate, but not cholesterol, reversed the statin-mediated decrease of pre-proET-1 mRNA levels. eNOS mRNA expression was reduced by oxidized LDL in a dose-dependent fashion (up to 57% inhibition), whereas native LDL had no effect. Statins were able to prevent the inhibitory action exerted by oxidized LDL on eNOS mRNA and protein levels. Hence, these drugs might influence vascular tone by modulating the expression of endothelial vasoactive factors.
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PMID:Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. 963 5


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