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

The author discusses a new concept of atherogenesis which is based on older hypotheses (lipid infiltration hypothesis), theory of impaired endothelial barrier, role of immunological and thrombocytic factors) and supplements it by new findings on the role of oxygen radicals in the development of atherosclerosis. The atherogenity of native low density lipoproteins (LDL) is enhanced substantially by their post-secretory changes caused by the action of free oxygen radicals on unsaturated fatty acids in the outer layer of LDL particles. The development of lipid peroxides on the surface of LDL leads to a changed orientation of the metabolism of LDL particles: oxidized LDL are not bound to classical LDL receptors in the liver but to so-called scavenger receptors in monocytes and macrophages. Lipid accumulation in monocytes, not controlled by feedback mechanisms, leads to formation of foam cells which are the basis of atheromatous plaques. This process can be influenced by antioxidants which block the formation of lipid peroxides. The new concept is particularly important for the population of Czechoslovakia and other formerly totalitarian countries where deterioration of the environment occurred and concurrently also adverse dietary changes (high fat, sucrose and spirit intake, low vegetable and fruit consumption). It is probable that an increased intake of antioxidants (ascorbic acid, carotenes, tocopherols, bioflavonoids, selenium etc.) would, along with other corrective provisions, suppress the steep increase of cardiovascular diseases.
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PMID:[A new concept of atherogenesis: the role of oxygen radicals]. 149 75

Nitric oxide is an important bioregulatory molecule, being responsible, for example, for activity of endothelium-derived relaxing factor (EDRF). Acute hypertension, diabetes, ischaemia and atherosclerosis are associated with abnormalities of EDRF. Nitric oxide is thought to be a retrograde messenger in the central nervous system. The technology is not yet available for rapid detection of NO released by a single cell in the presence of oxygen and/or nitrite, so the release, distribution and reactivity of endogenous NO in biological systems cannot be analysed. Here we describe a porphyrinic microsensor that we have developed and applied to monitoring NO release in a microsystem. We selectively measured in situ the NO released from a single cell with a response time of less than 10 ms. The microsensor consists of p-type semiconducting polymeric porphyrin and a cationic exchanger (Nafion) deposited on a thermally sharpened carbon fibre with a tip diameter of approximately 0.5 microns. The microsensor, which can be operated in either the amperometric or voltammetric mode, is characterized by a linear response up to 300 microM and a detection limit of 10 nM. Nitric oxide at the level of 10(-20) mols can be detected in a single cell.
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PMID:Nitric oxide release from a single cell measured in situ by a porphyrinic-based microsensor. 137 94

Cigarette smoking is the most preventable cause of cardiovascular morbidity and mortality. Smoking has been associated with a two-to fourfold increased risk of coronary heart disease, a greater than 70% excess rate of death from coronary heart disease, and an elevated risk of sudden death. These risks are compounded in the presence of hypertension, hypercholesterolemia, glucose intolerance, and diabetes, all of which exhibit a synergistic effect with smoking. The relationship between smoking and the risk of peripheral vascular disease has also been well documented. Smokers account for approximately 70% of patients with atherosclerosis obliterans and virtually all those with thromboangiitis obliterans. An association between smoking and cerebrovascular disease remains a matter of debate, although a higher risk of stoke and stroke-related mortality has been observed in smokers than in nonsmokers. Smoking has also been implicated in the development of cor pulmonale, but a direct association with congestive heart failure has not been established. Nicotine and carbon monoxide appear to play major roles in the cardiovascular effects of smoking. Both components adversely alter the myocardial oxygen supply/demand ratio and have been shown to produce endothelial injury, leading to the development of atherosclerotic plaque. Adverse effects on the lipid profile have been noted as well, but the relationship between these changes and the risk of cardiovascular disease remains to be confirmed. Notably, smoking cessation results in a dramatic reduction in the risk of mortality from both coronary heart disease and stroke. In light of the fact that the incidence of smoking has declined primarily among educated sectors of the U.S. population, future efforts must focus on providing effective education, including smoking cessation techniques, to the less-educated groups.
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PMID:Smoking and cardiovascular disease. 149 5

Nitroglycerin and the long-acting nitrates are widely used in all of the anginal syndromes and have proven effectiveness in relieving or preventing myocardial ischemia. Recent developments into nitrate mechanisms of action provide new insights as to the many anti-ischemic effects of these agents. Important concepts relating to coronary arterial endothelial function are germane to nitrate therapy. Endothelial-derived relaxing factor (EDRF) is presently believed to be nitric oxide (NO), which exerts vasodilatory and/or antiplatelet actions by increasing intracellular cyclic guanosine monophosphate as a result of activation of the enzyme guanylate cyclase. In the setting of coronary atherosclerosis, or even hyperlipidemia without histologic vascular disease, endothelial dysfunction may be present, promoting a vasoconstrictor/proplatelet aggregatory milieu. Nitroglycerin and the organic nitrates are NO donors; NO is the final product of nitrate metabolism, and in the vascular smooth muscle NO induces relaxation, resulting in vasodilation of arteries and veins. In the presence of inadequate EDRF production and/or release, it appears that nitroglycerin may partially replenish EDRF-like activity. Nitrates have long been known to have major peripheral circulatory actions resulting in a marked decrease in cardiac work. Venodilation and arterial relaxation result in a decrease in intracardiac chamber size and pressures, with a resultant decrease in myocardial oxygen consumption. In addition, a variety of direct coronary circulatory actions of the nitrates have been documented. These include not only epicardial coronary artery dilation, but the prevention of coronary vasoconstriction, enhanced collateral flow, and coronary stenosis enlargement. Recent work suggests that the nitrates may also act by preventing distal coronary artery or collateral vasoconstriction, which can reduce blood flow downstream from a total coronary obstruction. Thus, there are many anti-ischemic mechanisms of action by which nitroglycerin and the organic nitrates may be beneficial in both acute and chronic ischemic heart disease syndromes. The unique salutory effects of the nitrates in subjects with left ventricular dysfunction or congestive heart failure make these drugs particularly attractive for patients with abnormal systolic function and intermittent myocardial ischemia. Finally, the emergent role of intravenous nitroglycerin in acute myocardial infarction offers new prospects that nitrate therapy may prove to be beneficial in acute myocardial infarction as well as postmyocardial infarction for the reduction of left ventricular remodeling.
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PMID:Mechanisms of action of the organic nitrates in the treatment of myocardial ischemia. 152 24

It is generally recognized that formation of a platelet-fibrin-rich thrombus in an atherosclerotic coronary artery is the basis of unstable angina and acute myocardial infarction. Platelet hyperactivity has been identified in coronary risk factors such as hyperlipidemia and diabetes mellitus. Persistent activation of these cells results in release of growth factors that may contribute to the progression of atherosclerosis. Several recent studies show that endothelium, by generating or metabolizing a host of vasoactive substances, plays a critical role in the modulation of vascular tone. Important among these substances are prostacyclin (PGI2) and endothelium-derived relaxing factor (EDRF). The endothelium-dependent modulation of coronary artery tone correlates with the severity of atherosclerosis and the number of coronary risk factors. Procedures such as angioplasty and coronary bypass surgery injure the endothelium. The loss of endothelial smooth muscle relaxant function may contribute to the vasoconstriction and thrombosis often observed soon after these procedures. Thrombolysis (and subsequent reperfusion of the coronary artery) is also associated with severe endothelial dysfunction, with a resulting vasoconstrictor influence on the coronary vascular bed. Activation of leukocytes and their presence in the reperfused myocardium contribute to progression of myocardial injury by release of oxygen free radicals and proteolytic enzymes. Thus, it seems that a perturbation in this delicate equilibrium in cellular interactions relates to genesis and progression of myocardial ischemia.
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PMID:Platelet-leukocyte-endothelial interactions in coronary artery disease. 154 43

To elucidate the role of oxygen free radicals and lipid peroxidation in the pathogenesis of early hypertension and atherosclerosis, we studied the native distribution of three primary arterial antioxidant enzymes (AEs). Specific immunohistochemical localization of superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) was examined in the arterial wall of New Zealand White rabbits: six sham-operated normotensive/normolipidemics (NT/NL), seven coarctation-induced hypertensive/normolipidemics (HT/NL), eight normotensive diet-induced hyperlipidemics (NT/HL), and six hypertensive/hyperlipidemics (HT/HL). All three AEs were confined primarily to the endothelium in NT/NL rabbit aortas. However, in HT and HL rabbits a greater proportion of the arterial wall, including the endothelium, inner media, and middle media, displayed immunolocalization of three AEs. Multiple linear-regression analysis revealed that more than 70% of the total variability in the depth of immunolocalization of arterial AEs could be explained by changes in blood pressure and/or total cholesterol. Also, levels of plasma and arterial cholesterol oxides were significantly different (p less than 0.05) in HT and HL rabbits compared with controls, with twofold increases in NT/HLs, threefold increases in HT/NLs, and fourfold increases in HT/HLs. We conclude that intense free-radical activity in the arterial wall of HT and HL animals is one possibility and that this occurs despite the presence of abundant AEs.
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PMID:Immunolocalization of native antioxidant scavenger enzymes in early hypertensive and atherosclerotic arteries. Role of oxygen free radicals. 155 32

Consumption of carotenoids is associated with an enhanced immune response and protection against neoplasia and atherosclerosis. Because these effects have been achieved using carotenoids with no pro-vitamin A activity, they are assumed to be due to the antioxidant properties of carotenoids. Carotenoids protect against photosensitized oxidation by quenching singlet oxygen. In addition, beta-carotene reacts chemically with peroxyl radicals to produce epoxide and apocarotenal products. To investigate the potential significance of these reactions to biological systems, we have used soybean lipoxygenase to generate peroxyl radical enzymatically. beta-Carotene inhibits the oxidation of linoleic acid by soybean lipoxygenase as well as the formation of the hydroperoxide product. In addition, the absorption of beta-carotene is diminished (bleached) by soybean lipoxygenase. The potential significance of these antioxidant reactions of carotenoids to biological function is discussed.
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PMID:Carotenoids as cellular antioxidants. 157 92

Risk factors of tissue hypoxia was investigated in 26 patients with diabetic retinopathy (DMR), who compared with 62 patients without DMR. significant higher incidence of DMR was found in patients with poor diabetic control (HbA 1 greater than or equal to 10%), with orthostatic hypotension (OH), with peripheral neuropathy and with atherosclerosis respectively. Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) was lower (P less than 0.05) and venous oxygen tension in pedal dorsum (PvO2) higher (P less than 0.05) in DMR patients than those in uncomplicated DMR patients and normal subjects. There was a rank correlation between DMR severity and PvO2 (r = 0.429, P less than 0.05), which imply that decreased blood oxygen utilization may be related to diabetic microangiopathy. These data suggested that abnormal changes of HbA 1 and 2,3-DPG, decrease of peripheral blood oxygen utilization, atherosclerosis, OH and neuropathy might be risk factors of tissue hypoxia in DMR patients.
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PMID:[Study on risk factors of tissue hypoxia in patients with diabetic retinopathy]. 158 45

The effect of elastin peptides (kappa-elastin) was investigated on murine fibroblasts. The data indicate that elastin peptides increase the activities of antioxidant enzymes detoxifying free radicals and increase the lipid peroxide concentration within the cell. These results suggest that the influence of elastin peptides on oxygen metabolism may be related to their activities in vivo following elastin degradation and can contribute to their role in the pathogenesis of atherosclerosis.
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PMID:Effect of elastin peptides on the activities of antioxidant enzymes in fibroblasts. 159 27

The authors investigated the effect of hyperlipoproteinaemia on the formation of free oxygen radicals to which a significant role in the genesis of atherosclerosis is ascribed. They cause among others peroxidation of blood lipids with formation of lipoperoxides with a higher atherogenity. Using the method of luminol-dependent chemiluminiscence, their spontaneous and activated production in phagocytic blood cells was examined in a group of patients investigated on a long-term basis on account of hyperlipoproteinaemia (n = 24). The results were compared with a group of healthy subjects (n = 20); concurrently also blood lipids were examined. The authors revealed a statistically significant reduction of the spontaneous production of free oxygen radicals in the group of patients with hyperlipoproteinaemia. On examination of the activated production the drop of oxygen radical formation was at the borderline of statistical significance.
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PMID:[Free oxygen radicals in patients with hyperlipoproteinemia]. 163 91


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