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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 (ACE) inhibitors have played a highly beneficial role in the therapy of hypertension and congestive heart failure. Detailed analysis of some of the heart failure trials in patients with these diseases has uncovered unexpected benefits in the prevention of cardiovascular events. Paralleling these observations are the rapidly accruing basic studies describing important molecular and cellular effects of these agents. For example, ACE inhibition will prevent stimulation of smooth muscle cell angiotensin II receptors, thereby blocking both contractile and proliferative actions. In addition, ACE inhibition of kininase II inhibits the breakdown of bradykinin. Bradykinin is a direct stimulant of nitric oxide release from the intact endothelial cell. Thus, at the cellular level ACE inhibition shifts the balance of ongoing mechanisms in favor of those promoting vasodilatory, antiaggregatory, antithrombotic, and antiproliferative effects. These effects underlie the potential benefits of ACE inhibition in the therapy of coronary artery disease and atherosclerosis.
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PMID:Emerging concepts: angiotensin-converting enzyme inhibition in coronary artery disease. 911 53

Epidemiological and clinical studies have defined the lower incidence of atherosclerotic vascular disease in women than in age-matched men. After menopause the difference becomes less significant, what is due to estrogen deficiency. The mechanism of vascular protective effect of estrogen involves inhibition of smooth muscle cell proliferation, protection of endothelium function and improvement of lipid metabolism. One of the most important risk factor of atherosclerosis is hypertension. The prevalence of hypertension in elderly women is extremely high-up to 80%. Because of absence of the hormonal replacement therapy effect on blood pressure, there is an indication for antihypertensive therapy in postmenopausal women. Angiotensin-converting enzyme inhibitors are the class of drugs which can lower cardiovascular mortality due to hypertension and atherosclerosis in elderly women. They improve impaired insulin sensitivity and inhibit activation of renin-angiotensin system, both processes leading to the development of hypertension in postmenopausal women. Angiotensin-converting enzyme inhibitors also possess a direct anti-atherosclerotic properties, like inhibition of smooth muscle cell proliferation and migration, protection of endothelium function, reduced macrophages activation and foam cell accumulation, protection of LDL particles and improvement of fibrinolysis.
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PMID:[Treatment of hypertension in postmenopausal women]. 950 90

An increasing body of evidence indicates that impairment of endothelial function is crucially involved in the pathogenesis of cardiovascular disease. Injury to the endothelium precipitates atherosclerosis by causing smooth-muscle cell migration and proliferation, induction of expression of growth factors, and impairment of plasma coagulation and endogenous fibrinolysis. Angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists are widely used in patients with cardiovascular disease and have beneficial vascular effects beyond blood pressure control alone. Both exhibit a synergistic hemodynamic profile. Whereas calcium antagonists dilate large conduit and resistance arteries, ACE inhibitors inhibit the renin-angiotensin system (RAS) and reduce sympathetic outflow. Certain calcium antagonists, such as verapamil and diltiazem, reduce heart rate, whereas dihydropyridines tend to increase it. In the blood vessel wall, the local vascular effects of ACE inhibitors and calcium antagonists are complementary. ACE inhibitors diminish transformation of angiotensin I (Ang I) into angiotensin II (Ang II) and prevent degradation of bradykinin [which stimulates nitric oxide (NO) and prostacyclin formation]. Calcium antagonists inhibit the effects of Ang I and endothelin-1 (ET-1) at the level of vascular smooth muscle by reducing Ca2+ inflow and facilitating the vasodilator effects of NO. The resistance circulation is particularly dependent on extracellular Ca2+, thereby explaining why nifedipine and verapamil effectively inhibit ET-induced vasoconstriction in vitro and in vivo. In hypertension, ACE inhibitors and calcium antagonists markedly improve structural changes and increase the media/lumen ratio in resistance arteries. Long-term combination therapy with verapamil and trandolapril is particularly effective in reversing endothelial dysfunction in hypertensive animals. ACE inhibitors substantially reduce morbidity and mortality in patients with left ventricular dysfunction after myocardial infarction (MI). There is a strong trend indicating benefit with verapamil as well, but this is confined to patients with a normal left ventricular ejection fraction. Clinical studies have confirmed that calcium antagonists exhibit antiatherogenic properties. However, the clinical relevance of these findings has recently been disputed because short-acting dihydropyridines are reported to increase risk for MI. Because ACE inhibitors and calcium antagonists exhibit synergistic hemodynamic, antiproliferative, antithrombotic, and antiatherogenic properties, combination therapy provides a promising concept in patients with cardiovascular and renal disease.
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PMID:Combination of ACE inhibitors and calcium antagonists: a logical approach. 960 96

Angiotensin-converting enzyme (ACE) inhibitors have shown unexpected benefits in the prevention of ischemic events in patients with hypertension and congestive heart failure. In addition to these clinical observations, there is a growing body of knowledge about the molecular and cellular effects of ACE inhibitors. For example, ACE inhibition prevents stimulation of smooth muscle cell angiotensin II receptors, thereby blocking both contractile and proliferative actions. Angiotensin II blockade also diminishes the production of superoxide anion, which inactivates ambient nitric oxide. ACE inhibition of kininase II inhibits the breakdown of bradykinin, a direct stimulant of nitric oxide release from the intact endothelial cell. Thus, at the cellular level within the vasculature, ACE inhibition shifts the balance of ongoing mechanisms in favor of those promoting vasodilatory, antiaggregatory, antithrombotic, and antiproliferative effects. These effects underlie the potential benefits of ACE inhibition in the therapy of ischemia and atherosclerosis. Some data is available in humans to show that these effects can be sustained for months, thereby maintaining improved endothelial function and, presumably, allowing the initiation of steps that might alter the progression of atherosclerosis. Definitive information is not yet available in humans to show that ACE inhibition clearly alters the progression of atherosclerosis or diminishes coronary events in uncomplicated coronary disease. This promising area of investigation is, however, the subject of multiple clinical trials, which should provide clarification of this important question in coming years.
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PMID:Role of angiotensin-converting enzyme inhibition in reversal of endothelial dysfunction in coronary artery disease. 970 67

An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) has been associated with an increased risk of coronary artery disease (CAD) and myocardial infarction (MI). However, this finding has not been fully investigated in European populations with very low CAD risk. In a case-control study on a population from Southern Europe (Toulouse, France), we evaluated the ACE I/D polymorphism in 405 men, aged 35-65 years, who underwent coronary angiography and in 357 representative control men within the same age range. We also explored associations in the patients between this polymorphism and CAD severity. The ACE genotype was not associated with the presence of either CAD or MI. The ACE genotype was not a marker for angiographically assessed CAD severity. In a sample in one of the European populations with the lowest CAD risk, ACE I/D polymorphism was not associated with an increased risk for CAD or MI and did not influence the extent of CAD.
Atherosclerosis 1999 Jan
PMID:Angiotensin I-converting enzyme gene polymorphism in a low-risk European population for coronary artery disease. 992 May 24

Angiotensin-converting enzyme (ACE) inhibitors have been in clinical use for 20 years, during which time their application has been extended from the treatment of hypertension and heart failure to left ventricular dysfunction after myocardial infarction. They are also being used today for the treatment of diabetic nephropathy. More recently, the rationale for an antiatherosclerotic effect of ACE inhibition has emerged, based on more detailed understanding of the renin-angiotensin-aldosterone system and the role of this system in atherogenesis, in addition to supportive experimental animal and preliminary clinical data. The possible clinical benefit of ACE inhibition in atherosclerosis is currently being assessed in several large-scale trials with both surrogate and clinical outcome measures in high-risk patients with clinically manifest atherosclerosis, principally coronary artery disease. The trials should further elucidate the mechanisms of benefit from ACE inhibition and further define their role in therapy of patients with coronary disease.
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PMID:Towards 2001: will ACE inhibitors have a role in atherosclerosis treatment? 992 42

We investigated the effects of 6 months' treatment with the angiotensin-converting enzyme (ACE) inhibitor alacepril, given in low (100 mg/kg/d, p.o.) and high (200 mg/kg/d, p.o.) doses, on the development of atherosclerotic lesions in the aorta of monkeys fed a high-cholesterol diet for 6 mo. Mean blood pressures in the normal-diet group, high-cholesterol-diet group, and high-cholesterol-diet group treated with a low dose of alacepril were very similar, while that in the high-cholesterol-diet group treated with a high dose of alacepril was significantly reduced. The level of low-density lipoprotein in the high-cholesterol-diet group was significantly higher than that in the normal-diet group, and the levels in the alacepril groups were significantly lower than those in the high-cholesterol-diet group. Atherosclerotic lesions in the normal- and high-cholesterol-diet groups were 13.2 +/- 0.34% and 64.1 +/- 10.48%, respectively, and those in the groups treated with low and high doses of alacepril were 32.3 +/- 13.2% and 16.0 +/- 1.57%, respectively. Angiotensin-converting enzyme (ACE) activity in the thoracic aorta in the high-cholesterol-diet group was significantly higher than that in the normal-diet group, and the ACE activities in the alacepril groups were lower than that in the high-cholesterol-diet group. We conclude that alacepril prevents the development of atherosclerosis by reducing vascular ACE activity in monkeys given a high-cholesterol diet.
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PMID:Antiatherosclerotic effect of alacepril, an angiotensin-converting enzyme inhibitor, in monkeys fed a high-cholesterol diet. 1022 51

We analyzed the evolution with age of the frequencies of the I/D polymorphism of the angiotensin I-converting enzyme (ACE), a1166c of the angiotensin II AT1 receptor (AT1R), M235T of the angiotensinogen (AGT) and A225V of their methylenetetrahydrofolate reductase (MTHFR) gene in a healthy (H) population and the subsequent comparison to age- and sex-matched groups of myocardial infarction (MI) subjects. A total of 472 H subjects were divided into three groups < 30, 30-55 and > 55 years old and 277 individuals with MI into two groups 30-55 and > 55 years old. The evolution with age showed that the AGT M allele (P < 0.001) and the MTHFR V allele (P < 0.05) frequency decreased with age in H men. The comparison between healthy and MI groups showed that the MM genotype frequency increased in MI men > 55 years (OR =4.16; 95% CI; 1.72-10.1) The cc genotype showed a similar behaviour (OR = 3.96; 95% CI; 1.21-12.9). In men, all the combinations with MM genotype presented a high risk, with OR values between 1.10 and 7.22. In women, the cc genotype increased in the MI > 55 group (OR = 6.66; 95% CI; 2.02-21.9). All the combinations with the cc genotype showed OR values between 1.71 and 13.3. The MM genotype in men and cc genotype in men and women, are independent risk factors for MI. We propose that the study of the allele frequency evolution in an H population at different ages is essential to determine risk factors for MI in case-control studies, since data from isolated age-matched groups can be misinterpreted.
Atherosclerosis 1999 Aug
PMID:The genotype interactions of methylenetetrahydrofolate reductase and renin-angiotensin system genes are associated with myocardial infarction. 1048 56

Angiotensin-converting enzyme (ACE) inhibitors reduce the progression of atherosclerosis in animal models and reinfarction rates after myocardial infarction in humans. Although expression of components of the renin-angiotensin system has been reported in human coronary arteries, no data regarding their presence in carotid arteries, a frequent site for the occurrence of atherosclerosis plaques, are available. The following study sought to determine whether ACE mRNA and protein can be detected in human carotid atheromatous lesions. Twenty-four intact endarterectomy specimens were obtained from patients with severe carotid occlusive disease (17 males and 7 females, aged 68+/-1 years) and fixed within 30 minutes. Carotid artery specimens contained advanced Stary type V and VI lesions, and human ACE mRNA expression and protein were localized in cross sections by the combination of in situ hybridization and immunohistochemistry. Cell type-specific antibodies were used to colocalize ACE to smooth muscle cells, endothelial cells, macrophages, or lymphocytes. ACE protein was localized in the intima, whereas the overlying media was largely free of ACE staining. In less complicated lesions, ACE staining was modest and could be visualized in scattered clusters of macrophages and on the luminal side of carotid artery vascular endothelium. Smooth muscle cells were largely negative. ACE staining increased as lesions became more complex and was most prominent in macrophage-rich regions. The shoulder regions of plaques contained numerous ACE-positive macrophage foam cells and lymphocytes. In these areas, microvessels were positive for endothelial cell and smooth muscle cell ACE expression. However, microvessels in plaques free of inflammatory cells were stained only faintly for ACE expression. Labeling for ACE mRNA mirrored the pattern of protein expression, localizing ACE mRNA to macrophages and microvessels within the intima. In conclusion, atherosclerosis alters carotid artery ACE production, increasing transcription and translation within regions of plaque inflammation. These data provide another important mechanism by which inflammation associated with increased ACE expression may contribute to the progression of atherosclerosis.
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PMID:Angiotensin-converting enzyme expression in human carotid artery atherosclerosis. 1064 24

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1) receptor blockers share a number of common properties, including their ability to lower blood pressure. However, they can be differentiated based on their individual effects on the renin-angiotensin system, the fibrinolytic system and the actions of bradykinin. They act at different points in the cascade of events that constitute the renin-angiotensin system. In animal models of atherosclerosis, ACE inhibition was associated with a significant reduction in the percentage surface area of lesions, while no similar effect was evident with AT1 receptor blockade. In the fibrinolytic system, both ACE inhibition and AT1 receptor blockade were associated with reduced aldosterone levels, although the effect was greater with ACE inhibition; only ACE inhibition was associated with a significant reduction in plasminogen activation inhibitor-1. By blocking the degradation of bradykinin, ACE inhibitors potentiate the ability of bradykinin to reduce blood pressure and stimulate the release of tissue-type plasminogen activator from the vasculature, an effect not seen with AT1 receptor blockers.
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PMID:Pharmacology of ACE inhibitors versus AT1 blockers. 1090 25


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