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

There is mounting evidence that dysfunction of the renin angiotensin system is a vital contributor to the development of atherosclerosis. Nonetheless, the efficacy of angiotensin receptor blockers on clinical outcomes in patients with coronary atherosclerosis has been limited. This review will examine the potential mechanisms by which angiotensin receptor blockers potentially affect several key steps in the atherosclerotic process: endothelial function, inflammation, and thrombosis. Despite the mounting evidence for these agents on multiple processes in the development of atherosclerosis, their clinical utility in patients with coronary artery disease remains unclear.
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PMID:Mechanisms of benefit of angiotensin receptor blockers in coronary atherosclerosis. 1879 23

Metabolic syndrome (MS), which is composed of such factors as hyperinsulinemia, insulin resistance, glucose intolerance, abdominal obesity, arterial hypertension, and dyslipidemia, contributes to accelerated development of atherosclerosis, coronary artery disease, and type 2 diabetes. It has thus become one of the major public-health challenges worldwide. The primary goal of its clinical management is to reduce the risk for cardiovascular diseases related to atherosclerosis, especially myocardial infarction, stroke, and peripheral vascular disease, and to lower the risk for type 2 diabetes. The fi rst stage in its successful preventive management is identification of the population at high risk of developing metabolic syndrome. The therapeutic approach to metabolic syndrome consists fi rst of all of lifestyle modification, i.e. the introduction of a low calorie diet, weight reduction, and regular physical activity. For people at high risk for cardiovascular diseases and type 2 diabetes as well as those with coronary artery disease and/or type 2 diabetes, pharmacological therapy should be considered. Pharmacological management must address the multipathological process of metabolic syndrome, with each component identified and properly treated. Current therapies for metabolic syndrome treat fi rst of all obesity, insulin resistance, dyslipidemia, and hypertension. The pharmacological agents most often suggested are those which increase insulin resistance (metformin and thiazolidinediones). Among the medications used in metabolic syndrome therapy are also fibrates and statins for atherogenic dyslipidemia and those lowering blood pressure, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. This review presents the most important aspects of the prevention and treatment of patients with metabolic syndrome, including new therapeutic strategies.
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PMID:[Metabolic syndrome. Part III: its prevention and therapeutic management]. 1893 31

The presence of kidney disease, manifested by low glomerular filtration rates (GFR) and/or large amounts of protein in the urine, is independently associated with increased rates of cardiovascular disease (CVD). The severity of kidney disease is associated with graded increases in risk for CVD and death. Chronic kidney disease (CKD) should be recognized and treatment initiated early to maximize the chances for slowing nephropathy progression and reducing proteinuria. We recommend screening for CKD in all patients with CVD, including computing an estimated GFR and evaluating for proteinuria using a spot urine albumin:creatinine ratio. Aggressive management of traditional cardiovascular risk factors should be employed in this high-risk population, specifically rigorous hypertension control (including the use of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blocking agents (ARB)), management of hyperglycemia, hyperlipidemia and smoking cessation. Further studies are needed to identify the unique renal failure-related (non-traditional) risk factors that contribute to accelerated atherosclerosis in this population and performance of randomized trials to assess the effects of cardiovascular interventions in individuals with CKD.
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PMID:Cardiovascular disease in chronic kidney disease. 1912 39

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are thought to possess cardioprotective, cerebroprotective, and nephroprotective properties. Both classes of agents can prevent or reverse endothelial dysfunction and atherosclerosis, thereby potentially reducing the risk of cardiovascular events. Such a reduction has been shown with angiotensin-converting enzyme inhibitors in patients with coronary artery disease, but no such data are scarce with angiotensin receptor blockers (Valsartan in Acute Myocardial Infarction study). Both angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been shown to reduce damage in target organs, such as the heart and kidney, and to decrease cardiovascular mortality and morbidity in patients with congestive heart failure. These drugs (especially angiotensin receptor blockers) may successfully prevent atrial fibrillation and play a protective role in metabolic syndrome. In some clinical settings, combined therapy angiotensin-converting enzyme inhibitors with angiotensin receptor blocker (double blockade of the renin-angiotensin- aldosterone system) may appear the most effective.
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PMID:On target to dual block RAS? 1914 53

Premature atherosclerosis has been observed during the course of different systemic inflammatory diseases such as rheumatoid arthritis and sytemic lupus erythematosus. Remarkably, relatively few studies have been published on the occurrence of accelerated atherosclerosis in patients with vasculitis. In giant cell arteritis (GCA), mortality because of ischaemic heart disease is not increased. In addition, intima media thickness (IMT) is lower in patients with GCA than in age-matched controls. In contrast, IMT is increased significantly in Takayasu arteritis, another form of large vessel vasculitis occurring in younger patients. In Takayasu arteritis and in Kawasaki disease, a form of medium-sized vessel vasculitis, accelerated atherosclerosis has been well documented. In small vessel vasculitis because of anti-neutrophil cytoplasmic autoantibodies-associated vasculitis, cardiovascular diseases are a major cause of mortality. IMT measurements reveal conflicting results. During active disease these patients experience acceleration of the atherosclerotic process. However, when inflammation is controlled, these patients have atherosclerotic development as in healthy subjects. Several risk factors, such as diabetes and hypertension, are present more often in patients with vasculitis compared with healthy controls. In addition, steroids may be pro-atherogenic. Most importantly, many patients have impaired renal function, persistent proteinuria and increased levels of C-reactive protein, well-known risk factors for acceleration of atherosclerosis. Enhanced oxidation processes, persistently activated T cells and reduced numbers of regulatory T cells are among the many pathophysiological factors that play a role during acceleration of atherogenesis. Finally, autoantibodies that may be relevant for acceleration of atherosclerosis are found frequently in elevated titres in patients with vasculitis. Because patients have an increased risk for cardiovascular events, vasculitis should be treated with as much care as possible. In addition, treatment should be considered with angiotensin-converting-enzyme inhibitors and/or angiotensin receptor-1 blockers, statins and acetylsalicyl acid. Finally, classical risk factors for cardiovascular disease should be monitored and treated as much as possible.
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PMID:Translational mini-review series on immunology of vascular disease: accelerated atherosclerosis in vasculitis. 1930 50

The endothelium modulates vascular tone, blood coagulation, cell growth, and inflammation throughout the circulatory system. Endothelial dysfunction has been proposed to be one of the initiating events of atherosclerosis and is characterized by unbalanced concentrations of vasodilating and vasoconstricting factors, the most important being nitric oxide (NO) and angiotensin II (AII), respectively. In endothelial cells, AII, the key effector of the renin-angiotensin system (RAS), stimulates the production of reactive oxygen species (ROS) and negatively regulates the NO signaling pathway and thereby induces endothelial dysfunction. RAS blockade with an angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers(ARBs) provides a rational approach to reverse endothelial dysfunction. In this review, attention has been specifically focused on recent findings and putative mechanisms of the beneficial effects of RAS blockade on endothelial function.
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PMID:[Vascular endothelial dysfunction]. 1934 31

It is now widely accepted that redox signaling is a key feature in vascular homeostasis. Reactive oxygen species are generated by a wide range of enzymatic systems located in both vascular endothelium and vascular wall. Further, to their role as cytotoxic molecules produced by immune system, free radicals play critical signaling roles in the vascular wall. By regulating several redox-sensitive transcription pathways, free radicals play a key role in the synthesis of inflammatory mediators in both vascular endothelium and vascular wall, with important role in the overall vascular dysfunction. The well-established role of redox state in vascular disease mandates that development of newer therapeutic strategies should be able to alter redox-sensitive intracellular signaling events. Widely used cardiovascular agents like statins or angiotensin receptor blockers have well documented beneficial effects on vascular redox state, reflected also in clinical outcome improvement. Newer promising strategies along with recent patented inventions may also include thiazolidinediones, folates, tetrahydrobiopterin, cyclopentone prostaglandins and aldose reductase inhibitors with well known effects on vascular redox, but with still unclear results on clinical outcome. Better understanding of redox-sensitive intracellular signaling pathways could indicate the critical steps to intervene with newer agents to reverse vascular dysfunction, inhibiting atherosclerosis progression and potentially improve clinical outcome.
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PMID:Novel therapeutic strategies targeting vascular redox in human atherosclerosis. 1951 50

Endothelial dysfunction is a major determinant of atherosclerosis and a negative prognostic factor in patients with coronary artery disease and hypertension. Recovery of endothelial dysfunction has been associated with improved prognosis in these patients. The aim of the present study was to verify whether antagonism of angiotensin II AT1 receptors with an angiotensin receptor blocker, candesartan, improved endothelial function in patients with hypertension, stable coronary artery disease, and endothelial dysfunction. We studied 26 patients who were receiving beta-blockers with optimal blood pressure control, in a randomized, double blind study. Patients were randomized to placebo (n=13) or to candesartan 16 mg/d (n=13) for 2 months. Endothelial function was assessed by ultrasound using hyperemic flow-mediated dilation of the brachial artery. Mean arterial blood pressure was unchanged in both groups (from 93.3 +/- 9.2 to 93.2 +/- 17.3 mm Hg in the candesartan group and from 101.3 +/- 14.2 to 102.3 +/- 13.9 mm Hg in the placebo group; both P=ns). Maximal blood flow was similar between placebo and candesartan groups at baseline and at the end of the study, whereas flow-mediated dilation significantly increased in the candesartan group (from 5.27% +/- 1.69% to 7.15% +/- 2.67%; P=0.01) but remained unchanged in the placebo group (from 4.49% +/- 1.97% to 5.88% +/- 2.30%; P=ns). AT1 receptor antagonism with candesartan, in addition to b-blocker therapy, improves endothelial function in high-risk hypertensive patients.
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PMID:Effects of AT1 receptor antagonism with candesartan on endothelial function in patients with hypertension and coronary artery disease. 1953 23

Atherosclerotic cardiovascular disease is a major health problem worldwide. This article reviews studies clarifying the effects of gene-activating agents on the atherosclerotic vascular process, the occurrence of fatal and nonfatal atherosclerotic disease, and all-cause mortality. Studies originating in the 1970s linked drug-caused gene induction and high protein and cytochrome P450 concentrations in the liver with high apolipoprotein AI (apo AI) and HDL cholesterol (HDL-C) and reduced LDL cholesterol (LDL-C) levels in plasma and presented the view that the inducers, gene-activators, have beneficial exploitable effects against atherosclerosis. The following studies have shown that P450-enzymes respond to cholesterol accumulation and act in maintaining cholesterol homeostasis and that gene-activators act against the atherosclerotic process. The compounds include drugs indicated for dyslipidemias, such as statins, fibrates, niacin and cholestyramine, as well as compounds used for other purposes, including calcium channel blockers, angiotensin receptor blockers and glitazones. The compounds generate signaling mediators such as oxysterols and eicosanoids. The gene-activators upregulate, via the activation of nuclear receptors, genes encoding proteins such as apo AI and ATP-binding cassette (ABC) A1 transporters that efflux cellular cholesterol, transport it to the liver and excrete it into bile, and prevent cholesterol absorption in the intestine. Several statins, niacin, cholestyramine, calcium channel blockers, angiotensin receptor blockers, pioglitazone and etidronate regress atherosclerosis in coronary and /or carotid arteries. Other compounds, including fibrates, phenobarbital and alcohol also have positive antiatherogenic effects. Several gene-activators reduce mortality and / or morbidity from coronary heart disease and cerebrovascular disease, and also death from any cause.
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PMID:Gene-activators prevent and regress atherosclerosis and reduce mortality. 1960 43

Diabetes mellitus produces functional, biochemical and morphological myocardial abnormalities independent of coronary atherosclerosis and hypertension. Although tight glycemic control decreases the risk of heart failure in patients with diabetes, the effects of different diabetic treatment regimens on heart failure have yet to be determined and remain subject to further investigation.Evidence suggests that reactive oxygen species play an important role in the development of diabetic cardiomyopathy, and antioxidants have been used to reduce cardiomyopathy in patients with diabetes. Therefore, the present study examines the treatment of streptozotocin-induced diabetic rats with sodium selenite (5 mumol/kg/day, intraperitoneally). The results showed that sodium selenite treatment could restore the altered mechanical and electrical activities of diabetic rat hearts. The results also demonstrate that the beneficial effects of this treatment on diabetic rat heart dysfunction appear to be due to the restoration of diminished K(+) currents; the restoration of increased intracellular Ca(2+) concentrations in diabetes; and all these beneficial effects are partially related to the restoration of the cell glutathione redox cycle.It has been hypothesized that the angiotensin II (Ang II) signalling pathway may also play a role in the development of diabetic cardiomyopathy. It is the ability of Ang II to produce reactive oxygen species and the involvement of these molecules in signal transduction that are the hallmark of Ang II activation. Although action potential prolongation and diminished K(+) currents were reversed by angiotensin receptor type I (AT(1)) blockers in diabetic rat heart, their effects on Ca(2+) homeostasis in diabetic cardiomyocytes are not yet clear. Thus, the effects of AT(1) blocker treatment (candesartan cilexetil) on cardiac Ca(2+) metabolism, and on the contractile state and electrical activity of papillary muscle in diabetic rats were examined. It was shown that treatment with an AT(1) blocker restored the altered kinetics of Ca2+ transients in cardiomyocytes and the contractile activity in papillary muscle strips from diabetic rats. Thus, Ang II receptor blockade protects the heart from the development of cellular alterations that are typically related to diabetes.
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PMID:Altered mechanical and electrical activities of the diabetic heart: Possible use of new therapeutics? 1964 86


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