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 expression of CD143 (angiotensin-I-converting enzyme, ACE) in cardiovascular diseases may be an important determinant of local angiotensin and kinin concentrations. Much of the experimental and clinical evidence suggests a crucial role for Ang II in fibrogenesis and the development of atherosclerosis. Therefore, we have studied the distribution of CD143 in atherosclerotic and non-atherosclerotic segments isolated from different parts of the human vascular tree, including aorta and coronary, carotid, brachial, renal, iliac and femoral arteries, and staged according to the AHA. Two hundred and thirty native and formalin-fixed specimens of 80 patients were analysed by sensitive APAAP-technique using ten different monoclonal and polyclonal antibodies to human CD143 and several controls. In non-atherosclerotic segments or intimal thickening, CD143 was found almost restricted to the endothelial cells of adventitial arterioles and small muscular arteries. In contrast, a striking accumulation of CD143 was detected in all early and advanced atherosclerotic lesions. This de-novo occurrence of CD143 within the intimal vascular wall was caused by spindle-shaped subendothelial cells with macrophagic/histocytic features, activated macrophages and foam cells. In addition, advanced lesions of atherosclerosis showed a marked neo-expression of CD143 in newly formed intimal microvessels. Hypocellular fibrotic plaques depleted in microvessels and macrophages showed only little CD143. The de-novo occurrence of CD143 was dependent on the stage of atherosclerosis but not on its particular localisation within the vascular system. This early and obligatory CD143 expression at an unusual vascular site may contribute to unusual tissue levels of angiotensins as indicated by co-localisation of immunoreactive Ang II. Thus, it may be an important pathogenetic step in the development of atherosclerosis and an established target for pharmacological prevention.
Atherosclerosis 2000 May
PMID:CD143 in the development of atherosclerosis. 1078 32

In atherosclerosis numerous qualitative and quantitative changes in connective tissue metabolism parameters in serum and aorta occur. In atherosclerosis there is an enhanced activity of local renin-angiotensin systems. It leads to overexpression of ANG II, both in serum and arterial wall. ANG II stimulates SMC to over-synthesize the collagens type I and III. Hyper-cholesterolemia is a form of metabolic injury which can both induce phenotypic change of SMC and activate RA system in arterial wall. ACEI lower the accumulation of collagens type I and III, and enhance elastin content in arterial wall in experimental hypertension. The aim of this study was to assess the influence of captopril, enalapril and quinapril on connective tissue metabolism of the aorta in experimental hyper-cholesterolemia. 64 male New Zealand rabbits were used. Animals were fed with standard fodder, special diet (1% cholesterol content) or special diet + tested ACEI. Two doses of ACE inhibitors were used: 1st--equivalent to doses applied to human subjects (in mg/kg of body weight), 2nd--dose 10 times higher. The animals were divided into 8 equal groups: K--standard fodder, B--special diet, C1, C2--special diet + captopril in doses 2.5 and 25 mg/kg/24 hours, respectively, E1, E2--special diet + enalapril in doses 0.75 and 7.5 mg/kg/24 hours, respectively, Q1 i Q2--special diet + quinapril in doses 0.75 and 7.5 mg/kg per day, respectively. The experiment lasted for 6 months. After 24 weeks the animals were sacrificed and aortae were excised for collagens assay. The statistical analysis was performed using ANOVA, followed by LSD test; p < 0.05 was considered statistically significant. The aorta collagens content of cholesterol-fed rabbits significantly increased. The tested ACEI (captopril, enalapril in both doses and quinapril in lower dose) had a preventive effect against the increase of aorta collagen content.
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PMID:[The influence of angiotensin-converting enzyme inhibitors on collagen content of the aorta wall in experimental hypercholesterolemia]. 1080 May 84

The role of lipoprotein oxidation in promoting atherosclerosis is gaining recognition as its spectrum of effects is being unveiled. Accelerated atherosclerosis is a major cause of morbidity and mortality in diabetic patients. Treatment with ACE inhibitors reduces oxidation of low-density lipoprotein (LDL-ox) in hypertensive subjects, however, their effect on LDL-ox in diabetic patients is yet obscure. To evaluate the effect of the ACE inhibitor enalapril and the calcium channel blocker nifedipine on LDL oxidation in normotensive type 2 diabetic patients. A randomized single blinded cross-over study was conducted on 24 nonobese, metabolically stable, normotensive patients with type 2 diabetes who were randomly allocated to receive either enalapril, 10 mg/day, or nifedipine, 30 mg/day, for 4 weeks followed by a 2-week washout period. They were then crossed over to a 4-week course with the alternate drug. The oxidation of LDL was evaluated by three methods: dialdehyde analysis using the thiobarbituric acid reactive substances assay with and without the addition of CuSO(4) as well as determination of conjugated dienes in the LDL lipid extract. The propensity of the serum to oxidize LDL was reduced by enalapril by 17-28% depending on the laboratory method used (P=0.0001). Treatment with nifedipine resulted in a rise in LDL-ox of 7-11% as compared to baseline (P<0.05). The difference between the effects of enalapril and nifedipine was statistically significant with all three laboratory methods used (P=0.0001). Both drugs were equally effective in reducing systolic and diastolic blood pressure without affecting HbA(1c) levels and lipid profile. The albumin excretion rate was significantly reduced during treatment with enalapril returning to baseline levels during the washout period and the nifedipine treatment course. Our findings suggest that oxidation of LDL is attenuated by ACE inhibition and augmented by some calcium channel blockers. This observation may contribute insight into the underlying mechanism of the therapeutic effects of ACE inhibition in diabetic patients.
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PMID:Oxidation of low-density lipoprotein in normotensive type 2 diabetic patients. Comparative effects of enalapril versus nifedipine: a randomized cross-over over study. 1080 51

Transplant coronary artery disease is an accelerated vasculopathy that occurs in adult and pediatric heart transplant recipients, and it is a leading cause of death among late survivors. This form of coronary disease, also known as graft coronary disease, differs from classical atherosclerosis in both histologic and angiographic features and it progresses much more rapidly. Although its pathogenesis has not been determined precisely, both immune and non-immune mechanisms appear to contribute, with a final common pathway of endothelial injury due to both antigen-dependent and antigen-independent factors. Many investigators believe both cellular and/or humoral rejection play a direct role in its etiology. In children the true incidence of the condition is unknown, although a multicenter survey identified 58 (7.2%) patients among 815 transplant recipients at 17 centers. Detection remains difficult. In the past, non-invasive methods have been unsatisfactory, although recent experience has suggested that Dobutamine stress echocardiography may be promising. Once a diagnosis is made, treatment has been limited to palliation by either intracoronary interventional procedures or surgical coronary bypass grafting, and to cardiac retransplantation with its own set of problems. Current efforts are directed at prevention. Blood levels of cholesterol have been reduced in adults treated with Pravastatin, but there have been no reports of its use in children. In adults additional agents with potential benefit have included calcium channel blockers and ACE inhibitors. A multicenter trial in children is needed to answer the many remaining questions regarding transplant coronary disease in this age group.
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PMID:Transplant coronary artery disease in children. 1085 95

Angiotensin II (ANG II) has multiple effects on cardiovascular and renal cells, including vasoconstriction, cell growth, induction of proinflammatory cytokines, and profibrogenic actions. Recent studies provide evidence that ANG II could stimulate intracellular formation of reactive oxygen species (ROS) such as the superoxide anion (O2-). This ANG II-mediated ROS formation exhibits different kinetic and lower absolute concentrations than those traditionally observed during the respiratory burst of phagocytic cells, but it likely involves similar membrane-bound NAD(P)H-oxidases. Current evidence suggests that ANG II, through AT1-receptor activation, upregulates several subunits of this multienzyme complex, resulting in an increase in intracellular O2- concentration. ROS are involved in several signal pathways, and redox-sensitive transcriptional factors (AP-1, NF-kappaB) have been characterized. ANG II-induced ROS play a pivotal role in several pathophysiologic situations of vascular and renal cells such as hypertension, endothelial dysfunction, nitrate tolerance, atherosclerosis, and cellular remodeling. Although these perceptions suggest that drugs interfering with ANG II effects (ACE inhibitors, AT1 -receptor antagonist) may serve as antioxidants, preventing vascular and renal changes, the clinical studies are not so straightforward. In fact, only specific risk groups, such as patients with diabetes mellitus or renal insufficiency, may benefit from ACE inhibitors, whereas hard endpoints showed no advantage for ACE inhibitors in patients with essential hypertension.
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PMID:Free radical production and angiotensin. 1098 Nov 45

Arterial endothelial dysfunction is one of the key early events in atherogenesis, preceding structural atherosclerotic changes. It is also important in the late stages of obstructive atherosclerosis, predisposing to constriction and/or thrombosis. Endothelial function can be measured in coronary arteries and in the periphery by measuring vasomotor function after intra-arterial infusion of pharmacologic substances which enhance the release of endothelial nitric oxide. The disadvantage of these methods is their invasive nature, which generally makes them unsuitable for studies involving asymptomatic subjects. For this reason, noninvasive tests of endothelial function have been developed. In the most widely used of these, an ultrasound-based method, arterial diameter is measured in response to an increase in shear stress, which causes endothelium-dependent dilatation. Endothelial function assessed by this method correlates with invasive testing of coronary endothelial function, as well as with the severity and extent of coronary atherosclerosis. This noninvasive endothelial function testing has provided valuable insights into early atherogenesis, as well as into the potential reversibility of endothelial dysfunction by various strategies, including pharmacological agents (lipid lowering, ACE inhibition), L-arginine, antioxidants and hormones.
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PMID:Flow-mediated dilatation. 1106 34

The main etiology for mortality and a great percent of morbidity in patients with diabetes mellitus is atherosclerosis. A hypothesis for the initial lesion of atherosclerosis is endothelial dysfunction, defined pragmatically as changes in the concentration of the chemical messengers produced by the endothelial cell and/or by blunting of the nitric oxide-dependent vasodilatory response to acetylcholine or hyperemia. Endothelial dysfunction has been documented in patients with diabetes and in individuals with insulin resistance or at high risk for developing type 2 diabetes. Factors associated with endothelial dysfunction in diabetes include activation of protein kinase C, overexpression of growth factors and/or cytokines, and oxidative stress. Several therapeutic interventions have been tested in clinical trials aimed at improving endothelial function in patients with diabetes. Insulin sensitizers may have a beneficial effect in the short term, but the virtual absence of trials with cardiovascular end-points preclude any definitive conclusion. Two trials offer optimism that treatment with ACE inhibitors may have a positive impact on the progression of atherosclerosis. Although widely used, the effect of hypolipidemic agents on endothelial function in diabetes is not clear. The role of antioxidant therapy is controversial. No data have been published regarding the effects of hormonal replacement therapy on endothelial dysfunction in postmenopausal women with type 2 diabetes.
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PMID:Diabetes and endothelial dysfunction: a clinical perspective. 1115 15

The Joint European Societies--European Society of Cardiology, European Atherosclerosis Society and European Society of Hypertension--1998 recommendations on prevention of coronary heart disease (CHD) in clinical practice set priorities and goals. The top priority is patients with established CHD, or other atherosclerotic disease, because they are already under the care of cardiologists and are at high risk of further morbidity and mortality. The lifestyle goals are to stop smoking, make healthy food choices and be active physically. The risk factor goals are a BP < 140/90 mmHg, total cholesterol < 5.0 mmol/l (190 mg/dl) and LDL-cholesterol < 3.0 mmol/l (115 mg/dl). The appropriate use of prophylactic drug therapies--aspirin, beta-blockers, ACE inhibitors, lipid modification therapies and anticoagulants--is also a recommended goal. The final goal is to screen relatives of patients with premature CHD (men < 55 years and women < 65 years). Surveys of clinical practice such as EUROASPIRE (European Action on Secondary Prevention) have shown risk can be further reduced in patients with established CHD because many are not achieving these lifestyle and risk factor goals. So there is considerable potential to raise the standard of preventive care for coronary patients through more effective lifestyle intervention and the use of drug therapies with proven efficacy. For the patient, this will mean a longer life with better quality.
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PMID:The treatment potential in preventive cardiology. 1128 54

Type 2 diabetes mellitus is a prevalent disease in Westernised society, and more than 50% of individuals with diabetes mellitus die from cardiovascular causes. The underlying metabolic defect of type 2 diabetes mellitus is a combination of insulin resistance and decreased secretion of insulin by pancreatic beta-cells. Insulin resistance commonly precedes the onset of type 2 diabetes mellitus and is usually associated with a metabolic syndrome including hypertension, dyslipidaemia and obesity. Treatment of known cardiovascular risk factors, including hyperglycaemia, dyslipidaemia, hypertension and smoking, plays a key role in delaying the onset and progression of coronary heart disease (CHD) and other forms of atherosclerosis in patients with diabetes mellitus. Sulphonylureas should be used with caution in patients with CHD but aspirin (acetylsalicylic acid), beta-blockers and ACE inhibitors play an important role in the medical management of patients with established coronary artery disease and diabetes mellitus. Patients with diabetes mellitus represent a higher risk group of patients after both percutaneous and surgical coronary revascularisation and the decision regarding the choice of revascularisation procedure should take into account angiographic characteristics, clinical status and patient preference. Patients presenting with diabetes mellitus and acute myocardial infarction should be considered for reperfusion therapy with either urgent thrombolytic therapy or primary percutaneous coronary intervention.
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PMID:Optimisation of the management of patients with coronary heart disease and type 2 diabetes mellitus. 1139 41

Initial pharmacologic therapy for hypertension is low-dose thiazide diuretics, beta-blockers, and ACE inhibitors. Increasing data have confirmed that ACE inhibitors have specific benefit in patients with diabetes, atherosclerosis, left ventricular dysfunction, and renal insufficiency. CCBs are alternative agents for ISH in the elderly and appear to decrease stroke with perhaps less protection against progression of renal insufficiency and proteinuria, CAD mortality and new onset heart failure versus other initial agents, especially ACE inhibitors. ARBs are well tolerated and effective blood pressure lowering agents but have not been confirmed as effective as ACE inhibitors for reducing renal progression, clinical events, or mortality from heart failure. Effective pharmacologic antihypertensive therapy may avoid disabling and undetected cerebrovascular disease, cognitive dysfunction, and disturbing symptoms of elevated blood pressure. Vasopeptidase inhibitor, such as omapatrilat, and endothelin-1 antagonist, such as bosentan, may become future agents approved for the reduction of morbidity and mortality with hypertension. The ALLHAT trial continues to examine the potential benefits and harms of amlodipine versus chlorthalidone and lisinopril in a diverse high-risk population. Based on ALLHAT data, however, doxazosin is no longer an acceptable initial pharmacological agent. Intensive pharmacologic treatment with blood pressure lowering to less than 130/85 mm Hg is recommended with diabetes, renal insufficiency, and heart failure with additional goal of less than 125/75 mm Hg with renal failure and proteinuria greater than 1 g/24 h, based on multiple outcome studies.
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PMID:Update in pharmacologic treatment of hypertension. 1140 10


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