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)

The renin-angiotensin-aldosterone system (RAAS) is involved in the regulation of electrolyte and water balance primarily; however, it also influences vascular function and increases blood pressure--especially under pathological conditions. Hypertension, post-myocardial infarction state, and heart failure are, for example, associated with excessive systemic and/or local activation of the RAAS. Angiotensin II (AT-II) generated by the latter, contributes--along with additional factors and through its deleterious effects (vasoconstriction, endothelial dysfunction, atherosclerosis, prothrombotic state, fibrosis, etc.)--to damage to the target organs involved in the sequence of cardiovascular events. Inhibiting the RAAS at different levels is of therapeutic importance--its purpose is to delay disease progression, to prevent end organ damage, and to achieve a better outcome. As AT-II acts on several (AT1 and AT2) receptors, using angiotensin receptor blocking (ARB) agents with a high selectivity for the AT1 receptor is the rational choice. In view of its favourable therapeutic properties and efficacy demonstrated by morbidity and mortality studies, a generic formulation of appropriate quality, containing valsartan as active substance could prove to be the ideal treatment for patients with hypertension and other cardiovascular disorders.
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PMID:[The significance of generic valsartan in the treatment of patients]. 2171 Jul 9

The metabolic syndrome (MetS) is highly prevalent and confers an increased risk of diabetes and cardiovascular disease. A key early event in atherosclerosis is endothelial dysfunction. Numerous groups have reported endothelial dysfunction in MetS. However, the measurement of endothelial function is far from optimum. There has been much interest recently in a subtype of progenitor cells, termed endothelial progenitor cells (EPCs), that can circulate, proliferate, and dfferentiate into mature endothelial cells. EPCs can be characterized by the assessment of surface markers, CD34 and vascular endothelial growth factor receptor-2, VEGFR-2 (KDR). The CD34(+)KDR(+) phenotype has been demonstrated to be an independent predictor of cardiovascular outcomes. MetS patients without diabetes or cardiovascular diseases have decreased EPC number and functionality as evidenced by decreased numbers of colony forming units, decreased adhesion and migration, and decreased tubule formation. Strategies that have been shown to upregulate and enhance EPC number and functionality include statins, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and peroxisome-proliferator-activating-receptor gamma agonists. Mechanisms by which they affect EPC number and functionality need to be studied. Thus, EPC number and/or functionality could emerge as novel cellular biomarkers of endothelial dysfunction and cardiovascular disease risk in MetS.
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PMID:Dysfunctional endothelial progenitor cells in metabolic syndrome. 2194 28

Regulation of the fibrinolytic balance between plasminogen activators and inhibitors is modulated by the renin-angiotensin system (RAS). Impaired fibrinolytic function, characterized by increased plasminogen activator inhibitor type 1 (PAI-1) levels and decreased tissue plasminogen activator (t-PA) activity, has been found in patients with hypertension and may account in part for the increased risk of atherosclerosis and its clinical complications in these patients. In this regard, data from the literature indicate that different antihypertensive drugs may vary in their influence on fibrinolysis. Angiotensin-converting enzyme (ACE) inhibitors (ACE-I) have generally been shown to improve the fibrinolytic balance by reducing plasma PAI-1 levels. Calcium-channel blockers (CCB) have been reported to increase t-PA activity, and angiotensin receptor blockers (ARB) seem to be neutral in their effect. In the light of these data, this study aimed to compare the effects of ACE-I, ARB, and CCB on the fibrinolytic system in the early and late stages of the treatment in hypertensive patients. These data that the beneficial effect of RAS inhibition on fibrinolysis related to decrease in Ang II during early period of treatment. Amlodipine may also improve thrombogenic risk related to lowering the effect on increased platelet activation reflected by p-selectin. The greater improvement in the early and late stages of the fibrinolytic balance because of the combined action of RAS inhibition and Ca antagonism represents a further indication to the use of combinations of RAS inhibition (ACE-I or ARB) and CCB in the treatment of hypertension.
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PMID:Effects of lisinopril, irbesartan, and amlodipine on the thrombogenic variables in the early and late stages of the treatment in hypertensive patients. 2196 26

Cardiovascular risk reduction has been the target of several large clinical trials in the last decade. As the activation of the renin-angiotensin-aldosterone system (RAAS) plays a central role in the pathogenesis of atherosclerosis and cardiovascular disease, RAAS blockade has been suggested to be among the most efficient cardioprotective interventions, as revealed with the angiotensin converting enzyme (ACE) inhibitors trials. The angiotensin receptor blockers' (ARBs) efficacy in lowering blood pressure has been very well established. Telmisartan is however the first ARB to show a promising role in reducing cardiovascular risk in high-risk patients. This article will highlight the role of telmisartan in cardioprotection, underlying specifically the results of two major randomized controlled trials: ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomized AssessmeNt Study in aCE-iNtolerant subjects with cardiovascular Disease).
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PMID:Telmisartan and cardioprotection. 2214 Mar 19

Subclinical hypothyroidism (SH) is characterized by normal serum free T4 and free T3 levels and increased serum TSH levels. The relationship between SH and cardiovascular diseases has been one of the most popular topics recently. There is still some controversy concerning the cardiovascular impact of SH and management protocols. The vast majority of the studies published so far, suggests that SH accelerates endothelial dysfunction through traditional effects on risk factors that promote atherosclerosis and nontraditional effects on vasculature. In particular, SH is associated with increased of LDL-cholesterol, diastolic blood pressure, and markers of chronic inflammation (C reactive protein) and simultaneously reduces the bioavailability of nitric oxide to blood vessels and increases the expression of angiotensin receptor. Furthermore, replacement therapy seems to improve all these aspects.
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PMID:Endothelial dysfunction and subclinical hypothyroidism: a brief review. 2218 27

Type 2 diabetes mellitus (T2DM) is a disease characterized by inadequate beta-cell response due to progressive insulin resistance that typically accompanies physical inactivity and weight gain. T2DM is associated with substantial morbidity and mortality related to the associated atherosclerotic cardiovascular risks and diabetic vasculopathies, including microangiopathies (e.g., blindness and renal failure) and macroangiopathies (atherosclerosis). The increasing global prevalence of T2DM is linked to the rising rates of obesity, especially abdominal obesity. Visceral fat accumulation is upstream of obesity-related disorders including atherosclerotic cardiovascular disease (ACVD), and is associated with impaired insulin sensitivity and atherosclerosis through dysregulated production of adipocytokines, especially hypoadiponectinemia. This review article discusses the pathophysiological mechanisms responsible for T2DM and atherosclerosis, focusing on adiponectin. Clinical and experimental studies have shown that hypoadiponectinemia contributes to a variety of life style-related diseases including T2DM and atherosclerosis. It is likely that life-style modification, visceral fat reduction and use of medications that increase serum adiponectin levels (e.g., rimonabant, thiazolidinediones, fibrates, angiotensin receptor blocker and mineralocorticoid receptor blockade) when provided in combination can improve hypoadiponectinemia and thus prevent the development of life style-related diseases including T2DM and ACVD.
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PMID:Molecular mechanisms of diabetes and atherosclerosis: role of adiponectin. 2223 26

Oxidant stress plays an important role in the pathogenesis of atherosclerosis. In the late 1980s, biological studies demonstrated that oxygen-free radicals oxidize low-density lipoprotein-cholesterol, resulting in the creation of foam cells and inciting the cascade of biological events that ultimately result in the formation of atherosclerosis. In vitro studies showed the ability of antioxidant vitamins to scavenge free radicals and block the oxidation of low-density lipoprotein. This data was supported in vivo by early observational studies suggesting the benefit of antioxidants, particularly vitamin E, in the prevention of coronary artery disease. On the basis of these studies, the use of antioxidant supplements by the general population increased substantially and became a multibillion dollar industry. Despite strong biological evidence and promising observational data, more rigorous scientific evaluation did not support a causational relationship between vitamin supplements and lowering coronary artery disease risk. Several prospective, double-blind, placebo-controlled trials showed no benefit and possibly harmful effects. Therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and statins, which are known to have benefit in preventing and treating atherosclerosis by reducing blood pressure and cholesterol, also have a "pleiotropic" effect in reducing the formation of reactive oxygen species (ROS). Advances in molecular biology and the study of ROS led to a better understanding of the mechanisms that govern their production and role in atherogenesis. This progress identified unforeseen pathways by which these drugs favorably alter the balance in ROS production, and have raised possibilities for future targeted therapies in the prevention of atherosclerosis.
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PMID:Cardiovascular antioxidant therapy: a review of supplements, pharmacotherapies, and mechanisms. 2229 59

The saphenous vein remains the most widely used conduit for peripheral and coronary revascularization despite a high rate of vein graft failure. The most common cause of vein graft failure is intimal hyperplasia. No agents have been proven to be successful for the prevention of intimal hyperplasia in human subjects. The renin-angiotensin system is essential in the regulation of vascular tone and blood pressure in physiologic conditions. However, this system mediates cardiovascular remodeling in pathophysiologic states. Angiotensin II is becoming increasingly recognized as a potential mediator of intimal hyperplasia. Drugs modulating the renin-angiotensin system include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. These drugs are powerful inhibitors of atherosclerosis and cardiovascular remodeling, and they are first-line agents for management of several medical conditions based on class I evidence that they delay progression of cardiovascular disease and improve survival. Several experimental models have demonstrated that these agents are capable of inhibiting intimal hyperplasia. However, there are no data supporting their role in prevention of intimal hyperplasia in patients with vein grafts. This review summarizes the physiology of the renin-angiotensin system, the role of angiotensin II in the pathogenesis of cardiovascular remodeling, the medical indications for these agents, and the experimental data supporting an important role of the renin-angiotensin system in the pathogenesis of intimal hyperplasia.
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PMID:Role of the renin-angiotensin system in the pathogenesis of intimal hyperplasia: therapeutic potential for prevention of vein graft failure? 2244 45

Atherosclerosis is a highly complex biological process that has become the scourge of modern civilization. Endothelial dysfunction is the first step in the development of atherosclerosis. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the development of endothelial dysfunction and atherosclerosis. Several studies have shown that in vitro blockade of the RAAS is associated with improvement in markers of endothelial dysfunction and inflammation. Many clinical trials have demonstrated a clear benefit of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) manifested by a reduction of cardiovascular events. These findings suggest that ACEIs and ARBs can play an important role in prevention of atherosclerosis and in the delay of its progression. In this review we focus on the importance of RAAS blockade to prevent or delay progression of atherosclerosis and its impact on reduction of cardiovascular events.
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PMID:Effect of Angiotensin-converting enzyme inhibitors and Angiotensin receptor antagonists in atherosclerosis prevention. 2256 92

Cardiovascular diseases remain a major cause of morbidity and mortality worldwide, regardless of the recent advances in medical and surgical treatment, for as life expectancy in the developed countries increases, cardiovascular conditions affecting the elderly also rises. Atherosclerosis and cardiovascular diseases take a huge toll on the society, making them the leading cause of death in developed countries. Phenomenal advances in the pathophysiology of cardiovascular disease and the molecular signaling pathways has revealed the role of endothelial dysfunction involved therein and thus has raised the possibility of novel therapeutic targets. Such potential cellular targets include the vascular smooth muscle cells, monocyte/macrophage cell lines, platelets, and endothelial cells. Certain studies affirm that antiplatelet agents, antioxidant therapies, amino acid supplementation, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers may prevent or slow the progression of the disease process. The race is on for new medicines that can treat and prevent heart attacks and strokes, arising out of atherosclerosis, which kills nearly 1 million people a year in the U.S.A alone.
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PMID:Novel cardiovascular drugs in clinical trials. 2288 21


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