Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Increasing evidence supports an association between inflammation and plaque rupture. Macrophages and vascular smooth muscle cells are a source of cytokines and growth factors, which contribute to ongoing inflammation during atherogenesis. In a rabbit model of atherosclerosis, we evaluated the effect of the ACE inhibitor quinapril on different parameters implicated in the pathogenesis of the plaque, such as the presence of chemokines (interleukin-8, monocyte chemoattractant protein-1), collagen I, and vascular smooth muscle cell proliferation (PDGF-B). Since nuclear factor kappaB (NF-kappaB) has been implicated in the control of chemokine transcription and cell proliferation, we also investigated its activation and localization in the lesion. Quinapril administration for 28 days caused a down-regulation in arterial expression of interleukin-8 and monocyte chemoattractant protein-1 (mRNA and protein). However, collagen I expression (mRNA and protein) was not modified. PDGF-B expression was reduced in both the intima and the media. Active NF-kappaB, found in both macrophages and vascular smooth muscle cells, was also reduced by quinapril. Nevertheless, no significant changes were noted in the mild neointima formation, although a certain trend toward normalization was found in the quinapril-treated group. In conclusion, our results show that quinapril treatment attenuates several parameters associated with inflammation within the atherosclerotic lesions that are controlled by NF-kappaB, although it has no effect on collagen I expression. Both effects could contribute to the stabilization of the atherosclerotic plaque.
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PMID:ACE inhibitor quinapril reduces the arterial expression of NF-kappaB-dependent proinflammatory factors but not of collagen I in a rabbit model of atherosclerosis. 984 73

New insights from basic laboratory studies and clinical trials have raised the intriguing possibility that the renin-angiotensin-kinin system may play a critical part in the pathophysiology of atherosclerosis. These studies suggest the possibility of an important new therapeutic role for ACE inhibitors: reduction in the risk of atherosclerosis and the complications of coronary artery disease. Ongoing large-scale trials will establish whether the findings from basic laboratory studies and clinical heart failure trials will apply to patients with ischemic heart disease irrespective of the presence or absence of left ventricular dysfunction.
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PMID:Angiotensin-converting enzyme inhibition and vascular remodeling in coronary artery disease. 989 19

Hyperhomocysteinemia is a risk factor for arterial diseases, and the deterioration of the arterial elastic structures is one of the possible mechanisms underlying this epidemiological association. The aim of this paper is to quantitatively characterize such structural alterations and to explore their causes in a previous model of dietary induced mild hyperhomocysteinemia in minipigs. After four months, both a morphodensitometrical analysis of the elastic structure and a biochemical analysis of elastin and elastase activities were performed on the infrarenal abdominal aorta (IRAA) and the proximal left interventricular coronary artery (LIVCA) of control (C), hyperhomocysteinemic (H) and captopril-hydrochlorothiazide (Cp-Htz, 25 + 12.5 mg/d)-treated (H+/-Cp) minipigs (n = 8/group). Hyperhomocysteinemia was found to induce an increase in parietal elastolytic metalloproteinase activities. It resulted in opening and enlargement of fenestrae through the medial elastic laminae and in a decrease in medial elastin content (p < 10(-3)), expressed as well as volume density (%) as weight concentration (microg elastin/mg dry tissue). The thickness of the media and its basic lamellar organization was unchanged. The reduction in volume density was more dramatic in LIVCA (H: 4.7 +/- 0.9 vs C: 8.8 +/- 2.4), where it was evenly distributed within the media, than in IRAA (H: 6.7 +/- 1.1 vs C: 9.3 +/- 1.2), where the deep medial layers were less affected. Cp-Htz partly prevented the hyperhomocysteinemia-induced reduction of the medial elastin content in LIVCA (5.7 +/- 1.2) and IRAA (7.9 +/- 1.4). This effect, occurring in the subintimal layers of the media in both arteries but not in the deeper layers, resulted in a less beneficial effect in LIVCA than in IRAA. This result parallels the moderate beneficial therapeutic effect of ACE inhibitors against coronary atherosclerosis in humans. This paper reports for the first time a quantitative analysis of the arterial site-dependent deterioration of the elastic structure caused by mild hyperhomocysteinemia and the involvement of metalloproteinases in this process. These results confirm that the plaque-independent damage to elastic structure previously described in hyperhomocysteinemic-atherosclerotic minipigs was mainly due to homocysteine. This highlights that the metalloproteinase-related elastolysis and the subsequent structural deterioration is one of the major events underlying the epidemiological association between mild hyperhomocysteinemia and arterial diseases.
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PMID:Hyperhomocysteinemia induces elastolysis in minipig arteries: structural consequences, arterial site specificity and effect of captopril-hydrochlorothiazide. 992 50

The European Society of Cardiology, the European Atherosclerosis Society and the European Society of Hypertension published in 1994 a joint statement and recommendation on prevention of coronary heart disease in clinical practice. The EUROASPIRE study intended to investigate the present clinical practice in this respect in 9 European countries. The present paper deals with the Hungarian leg of the collaborative study. Hospital data of 546 patients below the age of 70 were reviewed of whom 29% were women. Consecutive patients were identified retrospectively with the following discharge-diagnoses: coronary bypass grafting, PTCA, acute myocardial infarction and angina pectoris. Minimum 6, in the average 18 month after the index event, patients were interviewed and examined. The participation rate was 77%. During the index hospitalisation an incomplete documentation of the main risk factors was found: blood pressure values were missing in 12%, lipid values in 48%, smoking status in 34%, body weight in 22% and family history in 46% of the cases, with wide variation between diagnostic categories. At follow-up 23% of the patients were obese (BMI > or = 30 kg/m2), 49% had elevated blood pressure (140/90 > or = Hgmm), 46% had total cholesterol above 5.5 mmol/l, 23% smoked and 27% were diabetic. 75% of the patients were on antiplatelet, 14% on anticoagulant, 58% on beta-blocking, 22% on lipid lowering, 32% on ACE-inhibitor and 44% on calcium channel blocking medication. The screening of first degree relatives was recommended in only 18% of the patients. The results speak for a substantial neglect of secondary prevention of coronary patients in the Hungarian clinical practice. However without complex detection, evaluation and management of risk factors it is impossible to reduce the recurrence and high mortality of coronary heart disease.
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PMID:[EUROASPIRE: survey conducted by the European Society of Cardiology on secondary prevention of coronary disease. Hungarian results]. 1006 78

Approximately 150 million people worldwide have diabetes mellitus, of whom 90% are type II diabetics. It is therefore of no surprise that diabetic nephropathy has become the leading cause of end-stage renal disease. Opposite to what has been known previously, kidney disease is at least as common in type II as in type I diabetes. However, because the majority of type II diabetics has hypertension for many years before diabetes mellitus becomes clinically relevant, renal lesions are often heterogeneous with frequent exclusive presence of ischemic changes. For the treatment of hypertension in diabetics without nephropathy (no microalbuminuria), drugs that exert beneficial effects or are at least neutral with respect to lipid and glucose metabolism, such as ACE inhibitors, angiotensin II-receptor antagonists, non-dihydropyridine-calcium channel blockers and the thiazide-like indapamide, are to be preferred. Although metabolically neutral, dihydropyridine calcium channel blockers should be used with caution, since an increase in cardiovascular morbidity and mortality in type II diabetics treated with these compounds has most recently been described. Once that diabetic nephropathy is established, blood pressure should be lowered to 120/80 mmHg (measured in seated position). Antihypertensive treatment should primarily be based on ACE inhibitors; angiotensin II-receptor antagonists are a valuable alternative if ACE inhibitors are not tolerated. Both ACE inhibitors and angiotensin II-receptor antagonists should be used with high caution in elderly patients with severe atherosclerosis in whom acute renal failure could occur due to the presence of bilateral renal artery stenosis. Newer studies indicate that non-dihydropyridine calcium channel blockers such as verapamil and diltiazem may be as effective as ACE inhibitors in preserving renal function in diabetic nephropathy. A fix-dose combination of the ACE inhibitor trandolapril with verapamil is now available; it should be reserved for patients whose blood pressure and/or proteinuria can not be adequately controlled with ACE inhibitors. Finally, indapamide is the only antihypertensive diuretic with nephroprotective properties.
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PMID:[Antihypertensive therapy in diabetes mellitus]. 1006 31

Morbidity and mortality in diabetes are caused mainly by its vascular complications, both in the microcirculation and in the large vessels. Diabetic nephropathy and retinopathy are the clinical hallmarks of microangiopathy, which may lead to end-stage renal failure and blindness. The cardiovascular complications in diabetes consist mainly of an accelerated form of atherosclerosis. Systemic hypertension is an early and frequent phenomenon. Nocturnal hypertension is also more frequent in people with diabetes compared with the nondiabetic population. Capillary hypertension has been demonstrated in type 1 diabetic patients. Poor metabolic control may induce elevation in blood pressure, but data are conflicting. The prevalence of white-coat hypertension in the diabetic population is comparable with that in the nondiabetic population. Prospective observational studies in type 1 and type 2 patients have revealed that abnormally increased urinary albumin excretion and other potentially modifiable risk factors--such as hypertension, smoking, poor metabolic control, and social class--predict increased all-cause mortality and cardiovascular mortality. Arterial hypertension is a risk factor in the initiation and progression of diabetic micro- and macroangiopathy. Diabetes, hypertension, and smoking are the three most important risk factors for fatal and nonfatal stroke. A randomized, double-blind, parallel study has revealed that the 5-year major cardiovascular disease rate was lowered by 34% for antihypertensive treatment compared with placebo. Furthermore, the study found a trend for lower all-cause mortality for low-dose antihypertensive-treated diabetic patients. Effective blood pressure reduction with ACE inhibitors and/or non-ACE inhibitors, frequently in combination with diuretics, reduces albuminuria, delays the progression of nephropathy, postpones end-stage renal failure, and improves survival in diabetic nephropathy.
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PMID:Diabetic hypertensive patients. Is this a group in need of particular care and attention? 1009 4

Long-term low density lipoprotein (LDL) apheresis using dextran sulfate cellulose (DSC) columns is a well tolerated treatment for drug refractory hypercholesterolemia with coronary heart disease (CHD). Hypercholesterolemic patients may benefit from LDL apheresis combined with cholesterol lowering drug therapy in terms of the prevention of the progression of atherosclerosis, stabilization of atheromatous plaque, and reduction of cardiac events. The major adverse reaction of LDL apheresis is temporal hypotension caused by hypovolemia or vasovagal reactions due to extracorporeal circulation. Anaphylactoid reactions in patients administered angiotensin converting enzyme inhibitors (ACE-I) are other dextran sulfate cellulose column related adverse reactions, which must be carefully prevented by ceasing the administration of ACE-I before LDL apheresis treatment. ACE-I must not be administered to patients undergoing LDL apheresis.
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PMID:Efficacy and safety measures for low density lipoprotein apheresis treatment using dextran sulfate cellulose columns. 1034 91

The vascular endothelium plays a key role in the control of vasomotor tone, local haemostasis and vascular wall proliferation processes. These responses are mediated by a variety of substances released from the endothelium in response to physiological stimuli, including prostacyclin, endothelin, and most importantly nitric oxide (NO). NO mediates vasodilation and furthermore inhibits platelet aggregation, expression of adhesion molecules for monocytes and adhesion of neutrophils, and it impairs growth of vascular smooth muscle cells. Risk factors for coronary atherosclerosis, such as hypercholesterolaemia, impair NO bioactivity, mainly due to an oxidative stress by superoxide radicals (O2-), which are able of rapidly inactivating endothelium-derived NO. Impaired NO bioactivity leads to unopposed paradoxical vasoconstriction of epicardial conductance vessels in response to physiological stimuli such as sympathetic activation as well as impaired vasodilator function of coronary resistance vessels. Therefore, endothelial dysfunction contributes to ischaemic manifestation of coronary artery disease. In addition, enhanced paradoxical vasoconstriction and a loss of endothelial antithrombotic activities might unfavourably modulate the course of acute coronary syndromes. Thus, the aim of therapeutic interventions is to increase NO bioavailability by either increasing NO production or decreasing O2- production in the endothelium. This goal can be reached, for example by ACE inhibitors, lipid-lowering drugs, increased shear-stress by physical exercise, oestrogens, and L-arginine, which have already been shown to improve endothelial vasodilator function. Nevertheless, it has to be determined whether ameliorated endothelial function will contribute to improved patients prognosis.
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PMID:Clinical importance of coronary endothelial vasodilator dysfunction and therapeutic options. 1035 93

Despite the (modest) regression observed in the MONICA study, coronary artery disease remains the leading cause of mortality in industrialised countries and it is worryingly progressive in emerging countries. Therapeutic progress has been considerable but only a small number of coronary patients benefit from it. The techniques are costly and justify efforts to improve selection of high risk patients. The results of the VA-HIT study, which demonstrated the importance of HDL cholesterol level in prevention, now raise the question of the optimal treatment of these patients and that of the association of fibrates and statins. The value of ACE inhibitors in the HOPE study in coronary artery disease was outstanding. In parallel, the efficacy of Mediterranean diet has been confirmed in secondary prevention as that of supplements of omega-3 fatty acids in the GISSI-Prevenzione study. When reference anti-anginal agents are ineffective in the most resistant forms of coronary artery disease, other classes of drugs have been shown to be effective in association. Finally, the theory of inflammation and infection of atherosclerosis has found new indirect arguments, whereas angiogenesis and vasculogenesis have been confirmed as the main leaders in the future treatment of coronary artery disease.
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PMID:[The best of coronary artery disease in 1999]. 1072 48

The Heart Outcomes Prevention Evaluation (HOPE) study found that the ACE inhibitor ramipril can lower the risk of atherosclerotic disease events and death in patients without heart failure but with known atherosclerosis or with diabetes plus at least one cardiovascular risk factor. This benefit was independent of ramipril's effect on blood pressure. Additional benefits were a reduced risk of diabetic nephropathy in diabetic patients, and a lower likelihood of newly diagnosed diabetes. On the other hand, vitamin E in the doses and duration studied (400 IU/day for 4.5 years) did not lower risk significantly.
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PMID:The HOPE study. Ramipril lowered cardiovascular risk, but vitamin E did not. 1078 Jan 1


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