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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The goals of rational antihypertensive medication should embrace the alleviation of atherosclerosis, the clinical consequences of which pose a major health problem and hence socio-economic concern for industrialized countries. Angiotensin converting enzyme (ACE) inhibitors are endowed with pharmacodynamic features which may help to attain this aim. Various animal experiments with cholesterol-fed rabbits, pigs and monkeys, as well as with rabbits with inherent disorder of lipid metabolism (WHHL-rabbit), demonstrated endothelial protection against loss of function due to hyperlipidemia and attenuation of lipid deposition in conduit blood vessels with ACE-inhibition. The alleviation of progressive atherosclerosis, which is a common feature of restenosis development following angioplasty, was shown in hypercholesterolemic rabbits and normal rats, but did not occur in clinically more relevant porcine models nor in large clinical trials. Circumstantial evidence from miscellaneous experiments is in line with the view that it is enhancement of bradykinin activity which causes the endothelial protection against the consequences of hypercholesterolemia. Furthermore, loss of relaxation of coronary resistance vessels without overt atherosclerosis despite hypercholesterolemia can be restored by augmentation of the EDRF-pathway as has been demonstrated with ramiprilat in vitro. This is being substantiated in preliminary clinical reports with different ACE-inhibitors. The possible association between improvement in both insulin sensitivity and endothelial function requires further investigation. The critical analysis of present experimental findings on a beneficial influence on both the spontaneous and the progressive development of atherosclerosis indicates ACE-inhibition to be more likely to preserve or restore the function of an intact endothelium than to interfere with the complex reaction occurring after injury of an already affected blood vessel.
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PMID:[ACE inhibition and atherosclerosis in the animal model]. 785 76

Endothelial function of epicardial arteries and coronary resistance vessels, as well as endothelial dysfunction and clinical symptoms of coronary artery disease and their therapeutic implications are reviewed including the presentation of the author's own results. Coronary endothelial vasodilator dysfunction represents a fundamental functional disturbance in vascular biology with the development of atherosclerosis. This functional alteration in coronary vascular reactivity appears to play an important integral part in the clinical presentation of coronary artery disease. Humoral and neuronal factors in favour of vasoconstrictor influences affect the balance between myocardial oxygen supply and demand, thus, facilitating the manifestation of myocardial ischemia. In order to identify more selective therapies the potential mechanisms underlying an impaired release or activity of EDRF/NO must be considered. Dysfunction of the endothelial L-arginine/NO pathway may involve decreased activity of NO synthase, increased inactivation of NO formed from its precursor L-arginine, impaired signal transduction mechanisms and reduced intracellular availability of L-arginine. Currently, initial therapeutic strategies include the supplementation of L-arginine, the use of antioxidants, as well as ACE-inhibitors. ACE-inhibitors have been shown not only to reduce vascular tone (and hypertrophy) by inhibition of angiotensin II formation, but also by increasing the endothelial production of NO and prostacyclin most likely due to the local accumulation of endothelium-derived bradykinin. Thus, ACE-inhibition appears to provide the potential to improve endothelial NO synthesis. Indeed, study results demonstrate that chronic ACE-inhibition is associated with an increased coronary blood flow response to acetylcholine suggesting an improvement in endothelial vasodilator functioning of coronary resistance vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coronary endothelial vasodilator dysfunction: clinical relevance and therapeutic implications. 785 84

Our appreciation of the vascular endothelium has changed considerably over the last decade. This organ, finally recognized as such, participates actively in vasomotor regulation and haemostasis. It secretes several relaxing and contracting factors which act locally to determine resting vascular tone. One of the relaxing factors, EDRF/NO plays an important physiological role as it contributes to the rapid adaptation of blood flow to various pharmacological and mechanical stimuli, thereby ensuring maintenance of adequate tissue perfusion. Nitric oxide (NO) is an ubiquitous factor which was crowned "molecule of the year 1992" by the scientific review Science. Its effects extend well beyond those on the cardiovascular system. Endothelial dysfunction is observed in many pathological states such as atherosclerosis, reperfusion injury, postangioplasty endothelial regeneration, degeneration of venous bypass grafts, pure spastic angina, hypertension and diabetes. It is associated with decreased production of EDRF/NO, which probably contributes significantly to the aggravation of endothelial and parietal lesions and to the natural progression of atherosclerotic disease in general. This article describes the principal vasoactive factors secreted by the endothelium and goes on to list the physiologic cardiovascular effects of EDRF/NO in detail, and to review the different pathologies associated with a disorder of secretion of this factor.
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PMID:[EDRF/NO and endothelial functions]. 801 Aug 61

The role of mental stress in ischemic heart disease is two-fold: as a risk factor of coronary artery disease and as a trigger of acute ischemic attacks in patients with established coronary atherosclerosis. The role of stress as a risk factor is still controversial. Data regarding the relationship between occupational factors and development of coronary atherosclerosis have not been confirmed. A type personality, above all when anger and hostility traits are present, seems to be a predisposing factor for the development of coronary artery disease. These data however, were not confirmed in study groups including patients with a higher prevalence of other, more important, risk factors. Stress can have an important role as a trigger of acute ischemic attacks. This is indirectly shown by the circadian distribution of the main manifestations of ischemic heart disease (sudden death, myocardial infarct, ST segment depression). In fact, their incidence is significantly higher in the morning hours, after awakening, when mental stress is higher. In the laboratory setting, mental stress can induce myocardial ischemia in a variable percentage of patients (0 to 80%). Prevalence of mental stress-induced myocardial ischemia varies depending on the stressor used, the patients group and, above all, the diagnostic tool. Ischemic episodes induced by mental stress, in fact, are generally silent and less severe and extensive than those elicited by exercise stress testing. It is therefore often necessary to use methods, such as myocardial scintigraphy, with higher sensitivity for the detection of myocardial ischemia in comparison with ECG. Patients with mental stress-induced myocardial ischemia tend to present higher scores on measures of aggressivity, anger and hostility. These psychological features are related to a hightened cardiovascular reactivity with a brisk and greater increase in heart rate and blood pressure after exposure to stress. It would be therefore useful to identify patients with such a behaviour by psychological assessment and/or analysis of sympatho-vagal balance by analysis of heart rate variability. The mechanism by which mental stress can induce myocardial ischemia is represented by an increase in myocardial oxygen demand, through the increased heart rate and blood pressure, probably associated with an increase in coronary vascular resistance. This last phenomenon is likely caused by small coronary vessel constriction mediated by alpha-adrenergic activation and by a reduced EDRF release by the damaged endothelium.
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PMID:[Stress and ischemic heart disease]. 802 44

Rupture of the lipid-rich atheromatous plaque, intraplaque hemorrhage, and intraluminal thrombus are three pathological hallmarks most commonly recognized in the infarct-related coronary artery at the site of acute myocardial infarction. Rupture of the atheromatous plaque is closely related to but does not fully explain the genesis of occlusive intracoronary thrombus formation and thus the development of acute myocardial infarction. Besides a variety of hematologic disorders, one should emphasize the role of the platelet-derived mediators that promote an environment where thrombosis and vasoconstriction occur, including TXA2, serotonin, ADP, platelet-derived growth factor, tissue factor, and the diminished availability of those natural endogenous substances that inhibit platelet aggregation, such as EDRF, tissue plasminogen activator, and PGI2. PGI2 released from vascular endothelial cells is extremely unstable. Our group provided the first evidence that HDL stabilizes PGI2 through the newly discovered function of Apo A-I, which is associated with the surface of HDL particles and identified as PGI2 stabilizing factor. Decrease in HDL-associated Apo A-I in patients with unstable angina and during the acute phase of myocardial infarction indicates that HDL plays an important role in preventing coronary atherosclerosis and intracoronary thrombus formation by stabilizing PGI2 in addition to the generally accepted biochemical property of HDL to prevent the accumulation of cholesterol by mobilizing free cholesterol from tissues or macrophages. There is also a PGI2 synthesis-stimulating factor in serum that has not yet been identified chemically. EDRF or nitric oxide provides another important regulating system in the vessel wall. Lipoproteins are inhibitors of endothelium-dependent relaxation of rabbit aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathogenesis of acute myocardial infarction. Novel regulatory systems of bioactive substances in the vessel wall. 804 17

Hypercholesterolemic and atherosclerotic coronary endothelial dysfunction consist of a progressive, not irreversible, impairment in reactions to various endothelium dependent relaxing substances in both the epicardial coronary artery and in the resistance vessel. Paradoxical vasoconstriction, dynamic stenoses and dysregulation of the coronary blood flow make this endothelial dysfunction contribute to the pathogenesis of myocardial ischemia. The selectivity of the impairment makes the concept of specific receptor operated signal transductions in hypercholesterolemia and low doses of oxidized LDL likely. In progressive atherosclerosis and high levels of oxidized LDL the dysfunction may spread to other receptors, the availability of L-arginine may decrease and the metabolism of EDRF change. Cholesterol-lowering therapy may restore this endothelial dysfunction. This paper will discuss the recent pathophysiological insights in dyslipidemic endothelial dysfunction and exposes the mode of action of various therapeutic drugs.
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PMID:Endothelial dysfunction and dyslipidemia: possible effects of lipid lowering and lipid modifying therapy. 805 97

Cardiac events are a major cause of death in dialysed patients. This is due, at least in part, to the high prevalence of atherosclerotic coronary heart disease. To a large extent, however, coronary lesions are acquired in the predialytic phase of chronic renal failure. The susceptibility of the heart to ischaemia is modulated by a number of factors, e.g. microvascular abnormalities, increased cardiac pulsatile workload, disturbed cardiac glucose metabolism, imbalanced autonomic innervation. The paradoxical result of there being no relationship of cardiac death in dialysis patients to blood pressure may be explained by confounding factors. Intradialytic hypotension appears to be an independent risk factor. The dialysis patient is exposed to hypertension and dyslipidaemia, two potent risk factors of atherosclerosis. Although no definite information is available, it is conceivable that factors related to dialysis procedures may also influence early or late events in atherogenesis. Such potential factors include oxidative modification of lipids, modulation of insulin resistance or glucose metabolism by non-insulin-dependent pathways, expression of adhesion molecules and activation of potential effector cells in atherogenesis, particularly monocytes and platelets, changes of synthesis and/or response to endothelin and nitroxide (EDRF), and possibly also accelerated formation of advanced plaques by hyperphosphataemia and/or hyperparathyroidism. Such proatherogenic mechanisms must be balanced against factors potentially protecting against atherogenesis; these comprise altered arachidonic acid metabolism (increased prostacyclin and decreased thromboxane synthesis), impaired platelet aggregation, antiatherosclerotic effects of heparin, and diminished concentrations of 1,25(OH)2D3, i.e. of a proatherogenic compound.
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PMID:Atherogenesis and cardiac death: are they related to dialysis procedure and biocompatibility? 806 10

Impairment of the vascular endothelium and its functions is a common sign of several serious diseases (atherosclerosis, hypertension, vascular spasms, thromboses) and is the initial stage of vascular affection in diabetes mellitus. The endothelium plays an important role in the transformation of some substances with a cardiovascular action and it secretes itself vasoactive substances. Vascular affections in diabetes are characterized by impaired homeostasis of vasoactive substances of endothelial origin--raised levels of vasoconstrictor factors (endothelins, thromboxanes) and reduction of vasodilatating factors (prostacyclin, EDRF--endothelin derived relaxing factor) as well as disorders of their interrelations. Vasoactive agents lead at the same time also to alteration of the growth and proliferation potential of smooth muscle cells of the vascular wall and thus to remodelling of the vascular structure in diabetes. At present possible ways how to influence these processes in a favourable way are intensely studied and discussed.
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PMID:[Endothelial dysfunction in diabetes mellitus]. 806 97

The vascular endothelium plays a vital role in the control of the circulation. It metabolizes various vasoactive substances, coverts angiotensin I to angiotensin II and secretes the potent vasodilators prostacyclin and EDRF (NO) and the vasoconstrictor peptide endothelin-1. The balance between these mediators determines the responses of the cardiovascular system in diseases such as hypertension, atherosclerosis and myocardial infarction.
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PMID:The Croonian Lecture, 1993. The endothelium: maestro of the blood circulation. 814 36

Hypercholesterolaemia and atherosclerosis impair responses to endothelium-derived nitric oxide (EDRF) in human and animal coronary arteries, a dysfunction that correlates with elevated low density lipoproteins (LDL). Previous studies show that native LDL immediately and reversibly inhibit acetylcholine-evoked EDRF responses in rabbit aortic ring precontracted with noradrenaline or serotonin whereas Cu(2+)-oxidised LDL (oxLDL) inhibit relaxations after 30 min with a potency that varies with the donor. We now show that antioxidants, probucol (10 microM) and ascorbic acid (100 microM) in vitro, prevent the inhibition by native LDL, indicating that this effect involves free radicals. As expected, the antioxidants had no influence on the inhibition by oxLDL. Superoxide dismutase appeared to have no effect on the inhibition by native or oxLDL. The oral administration of probucol to selected volunteers also prevented the inhibition of relaxation by their native LDL. These preparations showed a diminished susceptibility to oxidation and their oxLDL caused a markedly reduced and always reversible inhibition of relaxation compared to the potent and sometimes irreversible inhibition prior to administration of the drug. We conclude that antioxidants such as probucol reduce the formation of free radicals and the oxidative modification of LDL that lead to the impairment of EDRF responses and may prevent this same dysfunction in hypercholesterolaemia and atherosclerosis.
Atherosclerosis 1993 Oct
PMID:Probucol and other antioxidants prevent the inhibition of endothelium-dependent relaxation by low density lipoproteins. 828 Jan 87


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