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

For at least 60 years, spotty and poorly documented evidence has suggested that atherosclerotic disease in humans might be reversible. Little direct evidence was available until researchers demonstrated that rather advanced atherosclerotic lesions in experimental animals could show marked improvement after blood-lipid-reducing regimens that were often combined with other measures, such as increased ambient oxygen and estradiol therapy. In fact, this combination was used in this laboratory to produce one of the first effective regression studies in the rabbit model. In more recent studies in this laboratory, abundant evidence has been obtained that the advanced, eccentric, largely intimal lesions produced in the rhesus monkey are substantially reversible, and the much more inflammatory, concentric, and often transmural atheroarteritis induced by the same atherogenic ration in the cynomolgus monkeys is much more resistant to effective and beneficial regression. This unusual reaction appears to be due to the circulating immune complexes that participate in the pathogenesis of atherosclerosis in these cynomolgus monkeys, as well as possibly in a number of humans. The evidence for this phenomenon, as well as the varying effects of the lesions induced with contrasting food fats, is summarized in this presentation. Some of the time-related effects of varying interventions when the lesions are studied at 4-month intervals in rhesus and cynomolgus monkeys are also discussed. Other factors that may influence regression are also considered.
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PMID:Can atherosclerotic plaques regress? Anatomic and biochemical evidence from nonhuman animal models. 218 Feb 69

Beside the well-known risk factors for atherogenesis fibrinogen is an independent risk factor. High plasma fibrinogen levels predispose to hypercoagulability and thrombotic processes. Furthermore, rheological mechanisms, interfering with cell-to-cell contacts, and fluid-dynamic factors, facilitate local endothelial lesions resulting in atherosclerosis. Plasma fibrinogen, as the major contributing factor to plasma viscosity and red-blood-cell aggregation can limit oxygen supply and blood flow in microcirculation even in the absence of apparent coronary artery disease. Pharmacological interventions, in order to decrease elevated fibrinogen levels, do improve myocardial ischemia in patients with severe coronary artery disease.
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PMID:[The significance of rheologic mechanisms in atherogenesis]. 218 64

Rupture of an atherosclerotic plaque associated with partial or complete thrombotic vessel occlusion is fundamental to the development of ischemic coronary syndromes. Plaques that produce only mild-to-moderate angiographic luminal stenosis are frequently those that undergo abrupt disruption, leading to unstable angina or acute myocardial infarction. Plaques with increased lipid content appear more prone to rupture, particularly when the lipid pool is localized eccentrically within the intima. Macrophages appear to play an important role in atherogenesis, perhaps by participating in the uptake and metabolism of lipoproteins, secretion of growth factors, and production of enzymes and toxic metabolites that may facilitate plaque rupture. In addition, the particular composition or configuration of a plaque and the hemodynamic forces to which it is exposed may determine its susceptibility to disruption. Exposure of collagen, lipids, and smooth muscle cells after plaque rupture leads to the activation of platelets and the coagulation cascade system. The resulting thrombus may lead to marked reduction in myocardial perfusion and the development of an unstable coronary syndrome, or it may become organized and incorporated into the diseased vessel, thus contributing to the progression of atherosclerosis. In unstable angina, plaque disruption leads to thrombosis, which is usually labile and results in only a transient reduction in myocardial perfusion. Release of vasoactive substances, arterial spasm, or increases in myocardial oxygen demand may contribute to ischemia. In acute myocardial infarction, plaque disruption results in a more persistent thrombotic vessel occlusion; the extent of necrosis depends on the size of the artery, the duration of occlusion, the presence of collateral flow, and the integrity of the fibrinolytic system. Thrombi that undergo lysis expose a highly thrombogenic surface to the circulating blood, which has the capacity of activating platelets and the coagulation cascade system and may lead to thrombotic reocclusion. Measurements aimed at reversing the process of atherosclerosis via cholesterol reduction and enhanced high density lipoprotein activity are encouraging. Active research is being focused on the development of new antithrombotic tools, such as inhibitors of thrombin, thromboxane, and serotonin receptor antagonists, and monoclonal antibodies aimed at blocking platelet membrane receptors or adhesive proteins. These compounds may prove useful when immediate and potent inhibition of the hemostatic system is desired. Intensive research is still needed in the areas of pathogenesis and therapeutic intervention in atherosclerosis.
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PMID:Atherosclerotic plaque rupture and thrombosis. Evolving concepts. 220 64

Acetylcholine-induced constriction of human coronary arteries in vivo is commonly attributed to endothelial dysfunction. To examine the effects of 2 other important determinants of vascular responses--namely, agonist concentration and the segment of circulation under study--the diameters of proximal, middle and distal segments of the left anterior descending artery (LAD) and coronary sinus oxygen saturation were measured in 10 patients with angiographically normal coronary arteries (group 1) and in 7 patients with coronary atherosclerosis (group 2) after intracoronary acetylcholine was infused at concentrations from 10(-7)M to between 10(-4)M and 10(-2)M. In group 1, acetylcholine caused minor (less than or equal to 6%) but progressive dilatation of the LAD up to 10(-4)M, but constriction, particularly of the distal segments and tertiary branches, occurred at higher concentrations. Over the same concentration range, coronary sinus oxygen saturation rose progressively from a basal level of 36 +/- 3% to a maximum of 72 +/- 3% in the absence of changes in heart rate and blood pressure, suggesting marked progressive dilatation of resistance vessels. Concentrations greater than or equal to 10(-3)M caused intense constriction of distal epicardial vessels and, in some cases, anginal pain and objective signs of ischemia. Conversely, in group 2, acetylcholine (infused only up to 10(-4)M for ethical reasons) failed to cause significant changes in LAD diameter. These data suggest that the local acetylcholine concentration and coronary vascular segment under study may determine the observed response to at least an equivalent extent as does the presence or absence of coronary atherosclerosis, raising the question of whether a constrictor response to intracoronary acetylcholine reliably indicates the presence of coronary atherosclerosis.
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PMID:Response of angiographically normal and atherosclerotic left anterior descending coronary arteries to acetylcholine. 222 Jun 34

It is very important to elucidate the causative agents of atherosclerosis because coronary heart disease and cerebrovascular disease are the main causes of death in the developed countries. The evidence for a monoclonal origin of atherosclerotic plaques in humans prompted the study of the involvement of mutagens/carcinogens in the development of atherosclerosis. Polycyclic hydrocarbons, including 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene, were shown to act as initiators and/or accelerators in atherosclerotic plaque formation in the chicken, pigeon and mouse. Radiation and oxygen radicals were also demonstrated to be involved in the development of atherosclerosis in animals.
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PMID:International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 7/1/3. Animal studies suggesting involvement of mutagen/carcinogen exposure in atherosclerosis. 223 25

Based on the findings presented in this study, we propose the hypothesis that calcium could be a mediator for the development of atherosclerosis. Figure 8 shows a schematic illustration of the hypothesis. The presence of risk factors such as hypertension, hyperlipidemia, and smoking may increase the influx of calcium into vascular ECs. We have shown that reactive oxygen species, which are considered to be a risk factor for the development of atherosclerosis, actually increase [Ca++]i in vascular ECs. Increased intracellular calcium may damage the function of ECs, resulting in platelet aggregation at the damaged site. Increased intracellular calcium may also increase uptake of macromolecules in plasma such as fibrinogen and LDL, eventually forming atherosclerotic plaque. We have also shown that the influx of calcium into vascular ECs is associated with LDL transport across vascular ECs. The pretreatment by nifedipine inhibited both the increase in [Ca++]i and the increase in LDL transport, suggesting that intracellular calcium modulates LDL transport across ECs. Growth factors released from platelets may provoke migration and proliferation of medial SMCs in the aterial intima. It has been reported that migration of SMCs from arterial media to intima is enhanced by the presence of calcium, and can be inhibited by the pretreatment of calcium antagonist. As demonstrated in this study, calcium also plays an important role in the proliferation of SMCs provoked by some kinds of growth factors such as EGF. On the other hand, we found that an increased amount of dietary Mg suppressed the development of atherosclerotic lesions in the aorta of cholesterol-fed rabbits without affecting plasma total cholesterol and HDL-cholesterol concentrations. The mechanism of action might also be related to the calcium entry blocking action. The clinical and nutritional implications of these phenomena should be investigated further. The evidences presented in this study, however, would not be sufficient to fully explain the etiological role of calcium in atherogenesis. Further studies are required to elucidate the mechanism of the contribution of calcium to atherogenesis. The efficacy of calcium antagonist for the prevention of atherosclerosis in humans should also be investigated further.
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PMID:The role of calcium and magnesium in the development of atherosclerosis. Experimental and clinical evidence. 224 57

To test antiradical medicines effect the chemical production of singlet oxygen (NaClO + H2O2) was investigated. The quantity singlet oxygen chemiluminescence was decreased in the presence of Japanese Catalin and Chine Baineiting, antirheumatic Voltaren and less strong Finish Catachrome and Carnosine. American Quinax does not possess such an effect. One of the possible starting mechanisms causing different diseases (atherosclerosis, cataract etc.) is destruction of biomembranes by active forms of oxygen.
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PMID:[Decrease of singlet oxygen chemiluminescence by the presence of carnosine]. 229 61

The organism's oxygen balance was studied in 27 patients with atherosclerosis of the peripheral arteries during the test on a bicycle ergometer. The decrease in the patient's physical capacity was found to be in high correlation with the severity of oxygen disbalance.
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PMID:[Features of oxygen supply in exercise load in patients with atherosclerosis obliterans of the peripheral arteries]. 229 56

Vasodilation in normal and vasoconstriction in atherosclerotic coronary arteries have been observed in response to complex stimuli such as exercise and the cold pressor test. To study a single parameter that changes during these activities, and to better understand the pathophysiology of ischemia associated with increases in heart rate, we studied coronary vasomotion and blood flow response to increasing heart rate alone, produced by atrial pacing, with quantitative angiographic and Doppler flow-velocity measurements in 15 patients. In five patients with angiographically smooth coronary arteries (group 1), tachycardia produced progressive dilation of the epicardial artery with increases in cross-sectional area (CSA) of +15.5 +/- 3.4%, +22.4 +/- 2.1%, +28.5 +/- 3.3%, and +30.6 +/- 2.2% at 90, 110, 130, and 150 beats/min, respectively. In contrast, in five patients with mild angiographic narrowings (group 2), coronary segments failed to dilate with progressive tachycardia (-6.3 +/- 2.0%, -8.3 +/- 2.0%, -12.5 +/- 2.0%, and -11.4% at 90, 110, 130, and 150 beats/min, respectively), and progressive loss of luminal area was observed in five patients with severe angiographic narrowings (group 3) (-34.4 +/- 3.4%, -49.6 +/- 2.2%, -59.2%, and -72.8% at 90, 110, 130, and 150 beats/min, respectively). Coronary blood flow increased significantly with tachycardia in group 1 (+44.5 +/- 10.2%, +86.0 +/- 24.6%, +105.8 +/- 29.3%, and +137.5 +/- 46.0%), increased slightly in group 2 (+7.8 +/- 3.2%, +9.4 +/- 4.4%, +8.4 +/- 3.9%, and +10.0%), and decreased significantly in group 3 (-31.8 +/- 6%, -42.6 +/- 10.7%, -61.0%, and -70.0%). We conclude that an isolated increase in heart rate in patients with normal coronary arteries results in a modest increase in flow and vasodilation. In early atherosclerosis, the flow increase is blunted and dilation is replaced with paradoxical loss in luminal size. In patients with stenoses, further loss in luminal size occurs accompanied by a decrease in coronary blood flow. Thus, increasing heart rate alone in the setting of coronary stenoses could produce myocardial ischemia by a reduction in coronary supply, as well as by an increase in oxygen demand.
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PMID:Paradoxical narrowing of atherosclerotic coronary arteries induced by increases in heart rate. 230 22

Human LDL, HDL and lipoprotein deficient plasma isolated from 15 normal subjects was exposed to oxygen free radicals generated by gamma rays and the formation of peroxides and changes in levels of LDL alpha-tocopherol were measured. LDL exhibited an initial resistance against oxidation stress when compared to HDL. The results obtained for different individuals showed that there was no correlation between the initial levels of vitamin E in LDL or plasma and the amount of peroxide formed after exposure of the LDL to a standard quantity of oxygen radicals. Kinetic experiments with original LDL and LDL containing incorporated alpha-tocopherol demonstrated that the vitamin performed its antioxidant role by conferring some early protection to the lipids, being consumed in the process, but it was clear that additional factors are also instrumental in determining the total antioxidant potential of the human LDL.
Atherosclerosis 1990 Apr
PMID:Vitamin E content and low density lipoprotein oxidizability induced by free radicals. 235 Mar 69


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