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

Previous studies have shown that administration of angiotensin II to atherosclerosis-prone animal models results in an increase in the extent of atherosclerosis and that this effect may be independent of changes in blood pressure. We sought to determine whether atherosclerosis was increased in the setting of a low renin model of hypertension. Apolipoprotein E-deficient mice were made hypertensive using the deoxycorticosterone acetate salt model. We found that this resulted in a dramatic increase in the atherosclerotic lesion area in the setting of either a low- or high-fat diet. In the hypertensive animals, we observed an increase in angiotensin II staining that was localized to the adventitial macrophages. The increase in atherosclerosis was inhibited by administration of an angiotensin receptor antagonist, an angiotensin-converting enzyme inhibitor, or a renin inhibitor. In addition, blood pressure reduction, with either a calcium channel blocker or hydralazine, reduced the extent of atherosclerosis indicating an important contribution of the mechanical effects of elevated blood pressure. These data suggest that, even in the setting of hypertension that is not associated with activation of the systemic renin-angiotensin system, local generation of angiotensin II within the arterial wall may be of pathophysiological relevance to the development of atherosclerosis.
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PMID:Deoxycorticosterone acetate salt hypertension in apolipoprotein E-/- mice results in accelerated atherosclerosis: the role of angiotensin II. 1815 43

Activation of the renin-angiotensin system (RAS) is significant in the pathogenesis of cardiovascular disease and specifically coronary atherosclerosis. There is strong evidence that the RAS has effects on the mechanisms of action of atherosclerosis, including fibrinolytic balance, endothelial function, and plaque stability. Pharmacological inhibition of the renin angiotensin system includes angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and renin inhibitors. These agents have clinical benefits in reducing morbidity and mortality in the management of hypertension. In addition, ACE inhibitors and ARBs have shown to be effective in the management of congestive heart failure and acute myocardial infarction. This review article discusses the biochemical and molecular mechanisms involving the RAS in coronary atherosclerosis as well as the effects of RAS inhibition in clinical studies involving coronary atherosclerosis.
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PMID:Regulation of the renin-angiotensin system in coronary atherosclerosis: a review of the literature. 1820 Aug 12

Oxidative stress is a common denominator in many aspects of the pathogenesis of atherosclerosis and cardiovascular diseases. Some drugs, such as vitamin C, vitamin E, and a free radical scavenger, edaravone, are prescribed with oxidative stress as their main target. Furthermore, of the drugs in current clinical use, such as anti-hypertension reagents including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB), and anti-hyperlipidemic reagents like statins, protect various organs, e.g., vessel, brain, heart, and kidney, via anti-oxidative stress effects in addition to their original pharmacological properties. While results of clinical trials of anti-oxidative stress reagents in patients with cardiovascular disease are contradictory to date, this may be explained by a variety of reasons such as an inadequate study design. More competent anti-oxidative reagents are awaited, and superoxide dismutase mimetics, thiols, xanthine oxidase and NAD(P)H oxidase inhibitors, which regulate intracellular redox reaction and subsequently inhibit oxidative stress, are among promising candidates of future drug developments currently receiving much interest. In this review, the current advances will be highlighted in development of novel anti-oxidative therapeutic approaches against cardiovascular diseases.
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PMID:Oxidative stress in cardiovascular disease: a new avenue toward future therapeutic approaches. 1822 Oct 82

Advanced glycation endproducts (AGEs) are unavoidable byproducts of various metabolic pathways. They are formed by reactive metabolic intermediates such as methylglyoxal (MG), glyoxal, and 3-deoxyglucosone. These reactive intermediates bind to proteins, DNA, and other molecules and disrupt their structures and functions, which leads to different diseases such as vascular complications of diabetes, atherosclerosis, hypertension, Alzheimer's disease, and aging. In recent years, more compounds that prevent the formation of AGEs or degrade the existing AGEs have been produced and patented. They include: 1) aminoguanidine, 2) drugs used in the treatment of type 2 diabetes such as metformin and pioglitazone (patented), 3) angiotensin receptor blockers and angiotensin converting enzyme inhibitors, 4) pentoxyfylline (patented), 5) metal ion chelators desferoxamine and penicillamine, 6) antioxidants such as vitamin C or E, 7) amino group capping agents such as aspirin, 8) enzymes that cause deglycation of Amadori products, the Amadoriases, 9) compounds that mostly break alpha-dicarbonyl cross-links such as phenacylthiazolium bromide and its stable derivative ALT-711 (Alagebrium), and 10) derivatives of aryl ureido and aryl carboxaminido phenoxy isobutyric acids (patented). While some of these anti-AGE compounds are being used in clinical practice (such as metformin, pioglitazone, pentoxyfylline and aspirin) or tested in clinical trials (such as aminoguanidine and ALT-711), most of them are commonly used as experimental tools to investigate the role of AGEs in different disease conditions.
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PMID:Methylglyoxal and advanced glycation endproducts: new therapeutic horizons? 1822 Nov 7

The role of the renin-angiotensin-aldosterone system (RAAS) in many cardiovascular disorders, including hypertension, cardiac hypertrophy, and atherosclerosis, is well established, whereas its relationship with cardiac arrhythmias is a new area of investigation. Atrial fibrillation and malignant ventricular tachyarrhythmias, especially in the setting of cardiac hypertrophy or failure, seem to be examples of RAAS-related arrhythmias because treatment with RAAS modulators, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor blockers, reduces the incidence of these arrhythmias. RAAS has a multitude of electrophysiological effects and can potentially cause arrhythmia through a variety of mechanisms. We review new experimental results that suggest that RAAS has proarrhythmic effects on membrane and sarcoplasmic reticulum ion channels and that increased oxidative stress is likely contributing to the increased arrhythmic incidence. A summary of ongoing clinical trials that will address the clinical usefulness of RAAS modulators for prevention or treatment of arrhythmias is presented.
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PMID:The renin-angiotensin-aldosterone system (RAAS) and cardiac arrhythmias. 1845 94

Adiponectin is an adipocyte hormone that links visceral adiposity with insulin resistance and atherosclerosis. It is unique among adipocyte-derived hormones in that its circulating concentrations are inversely proportional to adiposity, and low adiponectin concentrations predict the development of type 2 diabetes and cardiovascular disease. Consequently, in the decade since its discovery, adiponectin has generated immense interest as a potential therapeutic target for the metabolic syndrome and diabetes. This review summarizes current research regarding the regulation of circulating adiponectin concentrations by physiological, pharmacological, and nutritional factors, with an emphasis on human studies. In humans, plasma adiponectin concentrations are influenced by age and gender, and are inversely proportional to visceral adiposity. In vitro studies suggest that adiponectin production may be determined primarily by adipocyte size and insulin sensitivity, with larger, insulin-resistant adipocytes producing less adiponectin. While adiponectin concentrations are unchanged after meal ingestion, they are increased by significant weight loss, such as after bariatric surgery. In addition, adiponectin production is inhibited by a number of hormones, including testosterone, prolactin, glucocorticoids and growth hormone, and by inflammation and oxidative stress in adipose tissue. Smoking decreases, while moderate alcohol consumption increases, circulating adiponectin concentrations. Dietary fatty acid composition in rodents influences adiponectin production via ligand-activated nuclear receptors (PPARs); however, current evidence in humans is equivocal. In addition to PPAR agonists (such as thiazolidinediones and fibrates), a number of pharmacological agents (angiotensin receptor type 1 blockers, ACE inhibitors, and cannabinoid receptor antagonists) used in treatment of the metabolic syndrome also increase adiponectin concentrations in humans.
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PMID:Physiological, pharmacological, and nutritional regulation of circulating adiponectin concentrations in humans. 1851 Apr 34

Renal artery stenosis (RAS) is usually caused by atherosclerosis or fibromuscular dysplasia. RAS leads to activation of the renin-angiotensin-aldosterone system and may result in hypertension, ischemic nephropathy, left ventricular hypertrophy and congestive heart failure. Management options include medical therapy and revascularization procedures. Recent studies have shown angiotensin receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACE-I) to be highly effective in treating the hypertension associated with RAS and in reducing cardiovascular events; however, they do not correct the underlying RAS and loss of renal mass may continue. Renal artery angioplasty was first performed by Gruntzig in 1978. The routine use of stents has increased technical success rates compared with angioplasty, and surgery is now only rarely performed. Although numerous case series claimed benefit in terms of blood pressure control, no adequately powered randomized, controlled, prospective study of renal artery interventions has reported their effect on cardiovascular morbidity or mortality. The CORAL trial, an ongoing study of renal artery stent placement and optimal medical therapy (OMT) funded by the National Institutes of Health, is the first study to attempt to do so. Until the CORAL trial results are in, physicians will continue to be faced with difficult choices when determining the optimal management for RAS patients and deciding which, if any, patients should be offered revascularization.
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PMID:The role of percutaneous revascularization for renal artery stenosis. 1859 3

The endothelium is characterized by a wide range of important homeostatic functions. It participates in the control of hemostasis, blood coagulation and fibrinolysis, platelet and leukocyte interactions with the vessel wall, regulation of vascular tone, and of blood pressure. Many crucial vasoactive endogenous compounds are produced by the endothelial cells to control the functions of vascular smooth muscle cells and of circulating blood cells. These complex systems determine a fine equilibrium which regulates the vascular tone. Impairments in endothelium-dependent vasodilation lead to the so called endothelial dysfunction. Endothelial dysfunction is then characterized by unbalanced concentrations of vasodilating and vasoconstricting factors, the most important being represented by nitric oxide (NO) and angiotensin II (AT II). High angiotensin-converting enzyme (ACE) activity leads to increased AT II generation, reduced NO levels with subsequent vasoconstriction. The net acute effect results in contraction of vascular smooth muscle cells and reduced lumen diameter. Furthermore, when increased ACE activity is chronically sustained, increase in growth, proliferation and differentiation of the vascular smooth muscle cells takes place; at the same time, a decrease in the anti-proliferative action by NO, a decrease in fibinolysis and an increase in platelets aggregation may be observed. AT II is then involved not only in the regulation of blood pressure, but also in vascular inflammation, permeability, smooth muscle cells remodelling, and oxidative stress which in turn lead to atherosclerosis and increased cardiovascular risk. Given the pivotal role exerted by AT II in contributing to alteration of endothelial function, treatment with ACE inhibitors or angiotensin receptor blockers (ARBs) may be of particular interest to restore a physiological activity of endothelial cells. In this view, the blockade of the renin-angiotensin system (RAS), has been shown to positively affect the endothelial function, beyond the antihypertensive action displayed by these compounds. In this review, attention has been specifically focused on an ARB, irbesartan, to examine its effects on endothelial function.
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PMID:Endothelial effects of antihypertensive treatment: focus on irbesartan. 1862 53

In the 1970s, pharmacological therapy interrupting the renin-angiotensin system was considered beneficial for patients with high-renin hypertension. This gave rise to the development of ACE inhibitors. Surprisingly, the ACE inhibitors proved to be effective not only in patients with high renin hypertension, but also in many patients with normal levels of plasma renin activity. At present ACE inhibitors have a significant position in a wide range of chronic illnesses such as atherosclerosis, hypertension, myocardial infarction, diabetic complications, stroke etc. They are combined safely with drugs like angiotensin receptor blockers, calcium channel blockers and thiazides with varying degree of benefits. Though they are safe drugs, patients need monitoring for renal insufficiency, hypotension, hyperkalemia etc. The safety of these drugs in paediatrics patients is not established. It is better to avoid these drugs during pregnancy.
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PMID:Therapeutic dimensions of ACE inhibitors--a review of literature and clinical trials. 1865 May 98

ONTARGET has established the efficacy of the angiotensin receptor blocker (ARB) telmisartan to slow disease progression and delay or prevent morbid events in patients with atherosclerosis. Although the study failed to confirm additive efficacy of telmisartan and the angiotensin-converting-enzyme (ACE) inhibitor ramipril, caution should be exercised in assuming that the mean response in a clinical trial applies to individual patients who might benefit from combination therapy. Physicians should also recognize that the design of the study, in which full doses of the ACE inhibitor and the ARB were administered, might not replicate clinical practice, where one drug is usually added to the other.
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PMID:Does the angiotensin receptor blocker telmisartan prevent morbid atherosclerotic events? 1866 35


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