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)

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

Dendritic cells (DCs) and renin-angiotensin system (RAS) have both been reported to contribute to the pathogenesis of atherosclerosis. Recently researches find the RAS expression on DCs and its effect on DCs' differentiation and proinflammatory function. The pattern of RAS expression on DCs derived from normal monocytes vs that on DCs derived from cornoary artery diease was investigated. In 82 coronary artery disease (CAD) patients and healthy controls (CTL), expressions of angiotensin I-converting enzyme (ACE), angiotensin AT1 receptor and DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) on DCs were measured by western-blot: CAD patients had an increased expression of ACE, AT1 receptor and DC-SIGN compared to controls especially in acute myocardial infarction (AMI). Cardiovascular risk factors of cardiovascular disease and circulating anigotensin II (Ang II) were assessed and found increased in AMI compared with CTL. The DC-SIGN and high-sensitivity C-reactive protein (hsCRP) also had significant correlations with RAS expression on DCs. Our research demonstrated the RAS expressions on DCs and their increase in CAD especially AMI. The RAS activation on DCs may cause a series of changes such as enhancing recruitment of DCs, activating the T cells and increasing their proinflammtory functions. The recruitment and T cells contact ability of DCs increases through DC-SIGN may be one of pathogenesis of atherosclerosis and this function may promoted by tissue RAS. CRP may also have some effect to the local RAS exprssion on DCs.
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PMID:Expression of renin-angiotensin system on dendritic cells of patients with coronary artery disease. 1966 95

Intracranial stenosis is a common etiology for ischemic stroke. Due to limitations of imaging studies, there are limited data on the prevalence of symptomatic and asymptomatic intracranial stenosis. Intracranial stenosis is more prevalent in Asian, Hispanic, and African-American populations. The reported proportion of patients with symptomatic intracranial stenosis among those hospitalized for ischemic cerebral events varies from 1% in non-Hispanic whites to as high as 50% in Asian populations. In population-based studies, the estimated prevalence of symptomatic intracranial disease varies from 1 in 100,000 for whites to 15 in 100,000 in African Americans. A Chinese population-based study reported intracranial stenosis in 7% of the population aged more than 40 years. Autopsy studies have noted intracranial atherosclerotic disease in about 23% of population in the 6th decade and 80% of population in the 9th decade of life. Angiotensin-converting enzyme polymorphisms, plasma endostatin/vascular endothelial growth factor ratio, glutathione S-transferase omega-1 gene polymorphism, and plasma homocysteine levels are non-modifiable risk factors noted to be associated with intracranial stenosis. Hypertension and serum lipid profile are major modifiable risk factors, whereas sickle cell disease is an uncommon risk factor that can be managed to reduce risk. Associations of intracranial atherosclerosis with diabetes mellitus, metabolic syndrome, Alzheimer's disease, aortic plaques, radiotherapy, and meningitis are less well documented.
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PMID:Epidemiology of intracranial stenosis. 1980 51

Angiotensin-converting enzyme inhibitors are effective at reducing blood pressure, whereas statins decrease plasma cholesterol impeding atherosclerosis. It is hypothesized that these medications may improve blood pressure and serum cholesterol by modifying the antioxidative status and energy metabolism of erythrocytes. In this study, the effects of 2 treatments are compared: lisinopril alone versus lisinopril + simvastatin, on erythrocyte antioxidant and energy metabolic enzymes. Patients with atherosclerosis and moderate hypertension are randomly assigned to receive lisinopril 10 to 20 mg/d or lisinopril 10 to 20 mg/d plus simvastatin 20 mg/d for 24 weeks. Higher catalase activity and lower glutathione peroxidase activity are observed in 94% to 100% patients from both groups after 12 and 24 weeks of treatment. Superoxide dismutase activity is increased significantly only after 24 weeks. No changes of glutathione reductase, lactate dehydrogenase, and phosphofructokinase activities are found under any conditions indicated. Both treatments decrease systolic and diastolic blood pressure equally. Only lisinopril + simvastatin treatment decreases plasma total cholesterol and low-density lipoprotein cholesterol. The results show for the first time that lisinopril monotherapy and combined lisinopril + simvastatin therapy exhibit specific and pronounced effects on antioxidant and energy metabolic enzyme activities in erythrocytes of hypertensive patients.
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PMID:Specific and pronounced impacts of lisinopril and lisinopril plus simvastatin on erythrocyte antioxidant enzymes. 1984 Nov 60

Angiotensin-converting enzyme (ACE) inhibitors improve outcomes in patients with coronary artery disease (CAD), heart failure, and hypertension. This short review examines clinical evidence for such effects and the underlying mechanism of action. One potential mode of action for ACE inhibitors in CAD is blood pressure reduction. However, recent data suggest that the effects of ACE inhibitors on the endothelium may also be relevant in attenuating the progression of atherosclerosis. In CAD, chronic overexpression of tissue ACE disrupts the angiotensin II/bradykinin balance with a net result of endothelial dysfunction, mainly due to an increased rate of apoptosis. An imbalance between endothelial apoptosis (death) and its renewal from the bone marrow (life) causes discontinuity of the endothelial layer, favoring the initiation and progression of a biochemical sequence that leads to atherosclerosis, plaque rupture, and eventually acute coronary syndromes. There is clinical and experimental evidence that ACE inhibition improves the life and death cycle of the endothelium. By restoring the bradykinin/angiotensin II balance, ACE inhibition reduces the rate of endothelial apoptosis and experimental results suggest that ACE inhibition can also improve the production and mobilization of endothelial progenitor cells from bone marrow. We report our experience in this context with perindopril.
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PMID:Secondary prevention of CAD with ACE inhibitors: a struggle between life and death of the endothelium. 2057 98

Angiotensin-converting enzyme inhibitors (ACE-i) and angiotensin II receptor blockers (ARBs) are of paramount importance in everyday clinical practice. Developed as antihypertensive drugs, they soon acquired another important indication as a result of their antiproteinuric activity and capacity to delay the progression of chronic kidney disease. ACE-i and ARBs started out being used as single drugs and were subsequently combined to obtain more complete blocking of the renin-angiotensin-aldosterone system (RAAS). The most evident advantages derived from the administration of these drugs - alone or in combination - have been obtained in proteinuric nephropathies, such as chronic glomerulonephritis and diabetic nephropathy, where they have become the treatment choice. Dual RAAS blockade has been recently evaluated in a large trial of high-risk cardiovascular patients, in whom no related benefits were shown. To the contrary, a higher risk of worsening renal function emerged. It is now quite clear that patients with high proteinuria levels are the ones that benefit most from RAAS inhibition, also with combined ACE-i and ARB. It is very important to pay the utmost attention when these drugs are used in patients in whom no benefit is obtained by RAAS inhibition, such as patients with chronic kidney disease and atherosclerosis, elderly patients, and those without any significant proteinuria.
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PMID:[Lights and shadows on single and dual RAAS blockade]. 2092 79

Angiotensin-converting enzyme inhibitors are effective at reducing blood pressure, whereas statins decrease plasma cholesterol, impeding atherosclerosis. The authors hypothesize that these medications may improve blood pressure by modifying the arginase-nitric oxide synthase system of erythrocytes. In this study, the effects of lisinopril alone versus lisinopril + simvastatin on erythrocyte and plasma arginase enzyme and nitric oxide metabolites are compared. Patients with atherosclerosis and hypertension are randomly assigned to receive lisinopril 10 to 20 mg/d or lisinopril 10 to 20 mg/d plus simvastatin 20 mg/d for 24 weeks. Higher arginase activity is observed in erythrocytes from 100% of patients and mainly recovered after 12 and 24 weeks of treatment with lisinopril or lisinopril + simvastatin. Plasma arginase activity is 3 orders of magnitude lower than erythrocyte arginase activity in all participants, suggesting a lack of its clinical significance. Both treatments cause the increase in plasma $$\hbox{ N }{\hbox{ O }}_{2}^{-}$$ , $$\hbox{ N }{\hbox{ O }}_{3}^{-}$$ , and $$\hbox{ N }{\hbox{ O }}_{2}^{-}$$ + $$\hbox{ N }{\hbox{ O }}_{3}^{-}$$ in 100% of patients. Erythrocyte $$\hbox{ N }{\hbox{ O }}_{2}^{-}$$ + $$\hbox{ N }{\hbox{ O }}_{3}^{-}$$ concentration is greatly decreased in hypertensive patients but recovers after monotherapy and combined therapy. The results show for the first time that lisinopril monotherapy and combined lisinopril + simvastatin therapy exhibit pronounced and equipotential normalizing effects on erythrocyte arginase and nitric oxide synthase activities.
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PMID:Impacts of lisinopril and lisinopril plus simvastatin on erythrocyte and plasma arginase, nitrite, and nitrate in hypertensive patients. 2140 1

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

The ultimate goal is to identify and target modifiable risk factors that will reduce major cardiovascular events in African American lupus patients. As a first step toward achieving this goal, this study was designed to explore risk factor models of preclinical atherosclerosis in a predominantly African American group of patients with systemic lupus erythematosus (SLE) using variables historically associated with endothelial function in nonlupus populations. Fifty-one subjects with SLE but without a history of clinical cardiovascular events were enrolled. At entry, a Framingham risk factor history and medication list were recorded. Sera and plasma samples were analyzed for lipids, lupus activity markers and total 25-hydroxyvitamin D (25 OH)D) levels. Carotid ultrasound measurements were performed to determine total plaque area (TPA) in both carotids. Cases had TPA values above age-matched controls from a vascular prevention clinic population. Logistic regression and machine learning analyses were performed to create predictive models. 25(OH)D levels were significantly lower, and SLE disease duration was significantly higher in cases. 25(OH)D levels inversely correlated with age-adjusted TPA. Angiotensin-converting enzyme (ACE) inhibitor nonuse associated with case status. Logistic regression models containing ACE inhibitor use, 25(OH)D levels and low-density lipoprotein levels had a diagnostic accuracy of 84% for predicting accelerated atherosclerosis. Similar results were obtained with machine learning models, but hydroxychlo-roquine use associated with controls in these models. This is the first study to demonstrate an association between atherosclerotic burden and 25(OH)D insufficiency or ACE inhibitor nonuse in lupus patients. These findings provide strong rationale for the study of ACE inhibitors and vitamin D replenishment as preventive therapies in this high-risk population.
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PMID:Premature atherosclerosis is associated with hypovitaminosis D and angiotensin-converting enzyme inhibitor non-use in lupus patients. 2222 38

Oxidative stress is a molecular dysregulation in reactive oxygen species (ROS) metabolism, which plays a key role in the pathogenesis of atherosclerosis, vascular inflammation and endothelial dysfunction. It is characterized by a loss of nitric oxide (NO) bioavailability. Large clinical trials such as HOPE and HPS have not shown a clinical benefit of antioxidant vitamin C or vitamin E treatment, putting into question the role of oxidative stress in cardiovascular disease. A change in the understanding of the molecular nature of oxidative stress has been driven by the results of these trials. Oxidative stress is no longer perceived as a simple imbalance between the production and scavenging of ROS, but as a dysfunction of enzymes involved in ROS production. NADPH oxidases are at the center of these events, underlying the dysfunction of other oxidases including eNOS uncoupling, xanthine oxidase and mitochondrial dysfunction. Thus NADPH oxidases are important therapeutic targets. Indeed, HMG-CoA reductase inhibitors (statins) as well as drugs interfering with the renin-angiotensin-aldosterone system inhibit NADPH oxidase activation and expression. Angiotensin-converting enzyme (ACE) inhibitors, AT1 receptor antagonists (sartans) and aliskiren, as well as spironolactone or eplerenone, have been discussed. Molecular aspects of NADPH oxidase regulation must be considered, while thinking about novel pharmacological targeting of this family of enzymes consisting of several homologs Nox1, Nox2, Nox3, Nox4 and Nox5 in humans. In order to properly design trials of antioxidant therapies, we must develop reliable techniques for the assessment of local and systemic oxidative stress. Classical antioxidants could be combined with novel oxidase inhibitors. In this review, we discuss NADPH oxidase inhibitors such as VAS2870, VAS3947, GK-136901, S17834 or plumbagin. Therefore, our efforts must focus on generating small molecular weight inhibitors of NADPH oxidases, allowing the selective inhibition of dysfunctional NADPH oxidase homologs. This appears to be the most reasonable approach, potentially much more efficient than non-selective scavenging of all ROS by the administration of antioxidants.
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PMID:Targeting NADPH oxidases in vascular pharmacology. 2240 85


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