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

Recent investigations of the complex interactions among vascular endothelium, platelets and leukocytes have relevance to the pathogenesis of atherosclerosis and ischemic heart disease. Perturbations in the hemodynamic equilibrium maintained by these cellular elements may lead to vasospasm, in vivo thrombosis and a reduction in blood flow. Recent advances in the understanding of these interactions in health and disease states are summarized. The effect of pharmacologic agents on these cell-cell interactions are discussed to provide the reader with a general understanding of the relevance of these interactions in cardiovascular disease.
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PMID:Endothelial, platelet and leukocyte interactions in ischemic heart disease: insights into potential mechanisms and their clinical relevance. 201 65

The authors present an up-to-date review on natural history of atherosclerosis. After a short introduction dealing with history of atherosclerosis research, data about morphology and pathology of the normal arterial wall are presented. Special attention is focused on structural differences of arteries in different body districts as well as vascular endothelium and smooth muscle cells and their role in atherogenesis. Pathogenetic mechanisms in the evolution of lesions and morphology of different types of atherosclerotic lesions based on cellular and metabolic changes are explained in details: early lesions such as gelatinous elevations-insudative lesions, fetty dots and streaks and microthrombi; advanced lesions such as fibromusculoelastic lesions, pearly-white fibrous atherosclerotic plaques and atheromatous plaques; and complicated lesions with calcifications, ulcerations, thrombosis and hemorrhage.
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PMID:[Pathophysiology of atherosclerosis. I. The morphology and developmental levels of atherosclerotic changes]. 220 74

We examined the hypothesis that impaired endothelium-dependent vasodilation in atherosclerosis is associated with decreased synthesis of nitrogen oxides by the vascular endothelium. The descending thoracic aortae of rabbits fed either normal diet, a high cholesterol diet for 2-5 wk (hypercholesterolemic, HC), or a high cholesterol diet for 6 mo (atherosclerotic, AS) were perfused in a bioassay organ chamber with physiologic buffer containing indomethacin. Despite a dramatic impairment in the vasodilator activity of endothelium-dependent relaxing factor (EDRF) released from both HC and AS aortae (assessed by bioassay), the release of nitrogen oxides (measured by chemiluminescence) from these vessels was not reduced, but markedly increased compared to NL. Thus, impaired endothelium-dependent relaxation in atherosclerosis is neither due to decreased activity of the enzyme responsible for the production of nitrogen oxides from arginine nor to arginine deficiency. Because the production of nitrogen oxides increased in response to acetylcholine in both hypercholesterolemic and atherosclerotic vessels, impairments in signal transduction are not responsible for abnormal endothelium-dependent relaxations. Impaired vasodilator activity of EDRF by cholesterol feeding may result from loss of incorporation of nitric oxide into a more potent parent compound, or accelerated degradation of EDRF.
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PMID:Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta. 225 62

There is increasing evidence that the vascular endothelium is an important functional component of the blood vessel wall, actively participating in normal vascular physiology as well as the pathogenesis of vascular diseases such as atherosclerosis. The localized modulation of vascular endothelium to a nonadaptive functional state can be termed endothelial dysfunction. This article provides a brief overview of the multiple vital functions of endothelium, and a working concept of endothelial dysfunction especially as it relates to atherosclerosis and its thrombotic complications.
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PMID:Endothelial dysfunction and atherosclerosis. 251 96

Understanding the mechanisms involved in maintaining the integrity of the vascular endothelium is fundamental to studies on atherosclerosis, thrombosis, inflammation and tumor invasion. One of the essential aspects is the relationship between the endothelial cell (EC) layer and the underlying components of the basement membrane (BM). The importance of the biological role of the individual components of the BM in the promotion of EC adhesion is investigated. In this study suspensions of bovine corneal ECs (BCECs; 5 x 10(4)/ml) were used to investigate the adhesion of EC to collagen type IV and a mixture of fragments of the tetrameric molecule (IV-F, consisting of 75, 120 and 140 kD fragments), as well as collagen types I and III, coated at a 10-micrograms/ml concentration onto glass coverslips in vitro. Adhesion was quantified after 2 h of interaction by direct counting in the light microscope following fixation of the adherent cells. Collagens type IV and IV-F markedly promoted BCEC adhesion both in the presence or absence of 10 or 50% fetal calf serum, indicating that the integrity of the tetrameric molecule is not required for EC adhesion to collagen type IV, but can be replaced by high molecular weight fragments. Collagens type I and III increased EC adhesion in the absence of serum, although not in the presence of serum. Indirect evidence for a possible role of fibronectin in EC adhesion to type-IV collagen is given by the ability of the tetrapeptide (Arg-Gly-Asp-Ser (10 micrograms) to temporarily block (15-30 min) the adhesion-promoting effect of type-IV collagen. The nature of the adhesion sequences on the fragments of type-IV collagen remains to be elucidated.
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PMID:Interaction between endothelial cells and basement membrane components. In vitro studies on endothelial cell adhesion to collagen types I, III, IV and high molecular weight fragments of IV. 253 76

High circulating plasma levels of free fatty acids may injure endothelial cells, resulting in decreased barrier function of the vascular endothelium. The effect of media supplementation with varying concentrations of either linoleic (C18:2 omega 6) or linolenic acid (C18:3 omega 3) on albumin transfer across cultured endothelial monolayers was studied. A 24-h cell exposure to linoleic but not linolenic acid resulted in a concentration dependent and largely reversible increase in albumin transfer. Both fatty acids and in particular linolenic acid incorporated into cellular phospholipids. In contrast, only supplementation with linoleic but not linolenic acid resulted in an increased incorporation of this fatty acid into cell triglycerides. Similarly, only total cell triglyceride content increased after incubation with linoleic- but not with linolenic-enriched media. These results indicate that cellular enrichment with linoleic but not linolenic acid causes cellular perturbations that may be implicated in atherosclerosis.
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PMID:Linoleic acid and linolenic acid: effect on permeability properties of cultured endothelial cell monolayers. 256 26

Age is strongly correlated to the onset of atherosclerotic lesion formation in humans. This may be associated with an age-related increase in the susceptibility of the vascular endothelium to oxidative injury. Such injury may result in altered endothelial function as a barrier to plasma components, such as cholesterol-rich lipoprotein remnants. To investigate this hypothesis, the relationship between endothelial cell culture age, susceptibility to oxidative injury and protection against this injury by the nutrient/antioxidant vitamin E on endothelial barrier function (transfer of albumin across endothelial monolayers) was examined. An acute 24 h exposure to 30 microM linoleic acid hydroperoxide resulted in increased albumin transfer at all cell passages tested (up to passage 50). Pre-enrichment of cells with 25 microM vitamin E always protected endothelial cells against oxidized fatty acid-induced cell injury, independent of cell age. In comparison, patterns of total cell protein and DNA were not markedly influenced by experimental treatments, although age-related declines in total DNA were noted. These data suggest that the possible correlation between age and the onset of atherosclerosis may be in part related to a decrease in endothelial barrier function due to oxidative stress, permitting more blood components to enter the arterial wall. Furthermore, vitamin E may protect endothelial cells against oxidant-mediated vascular injury.
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PMID:Protective effects of vitamin E in age-related endothelial cell injury. 259 93

The recent discovery of endothelium-derived relaxation factor (EDRF) has altered the traditional classification of vasodilators used in angina pectoris and heart failure. If a vasodilator induces release of EDRF from the epithelium it is classified as endothelium-dependent, if not it is independent. Sodium nitroprusside and SIN-1 (active metabolite of molsidomine) are the main independent vasodilators since the endothelium relaxation factor appears to be principally a nitric oxide radical in these synthetic vasodilators. In contrast, calcium-channel blockers and a good number of endogenous chemical mediators (acetylcholine, bradykinin, serotonin, etc.) are endothelium-dependent. Furthermore, simple increase in blood flow through the large vessels can result in endothelium-dependent vasodilation (flow rate-dependence) the extent of which depends on the drug examined. The fact that the pharmacologic response of a vasodilator can be altered under certain pathologic conditions (atherosclerosis, hypertension, diabetes, etc.) further increases the importance of the role of the vascular endothelium in the action of vasodilators since endothelial modulation may then be completely diverted to secretion of endothelium-derived contracting factors (EDCFS).
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PMID:[Vasodilator agents and the vascular endothelium]. 262 13

Significant advances have been made in our understanding of the role of the vascular endothelium in preventing thrombosis and in decreasing vascular spasm. The endothelium provides a surface receptor, thrombomodulin, that binds thrombin. In this form, thrombin loses its ability to clot fibrinogen or to aggregate platelets, but is able to activate protein C. In its activated state, protein C is able to act as an inhibitor of coagulation by virtue of its proteolytic destruction of Factors Va and VIIIa. Congenital deficiency of protein C is associated with early and recurrent thrombosis. The discovery that the endothelium is responsible for the production of a short-acting inhibitor of smooth-muscle contraction (EDRF) was a remarkable advance. One of the EDRF substances has been demonstrated to be NO, which has inhibitory effects on both smooth muscle and blood platelets. Activity of EDRF appears to be diminished or lost as a consequence of atherosclerosis, and stimuli that cause vasodilation via the EDRF pathway in normal vessels cause vasoconstriction in atherosclerotic arteries. Regression of atherosclerosis in experimental animals appears to be associated with restoration of EDRF activity.
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PMID:The endothelium, platelets, and coronary vasospasm. 264 64

Watanabe heritable hyperlipidemic (WHHL) rabbits have elevated concentrations of plasma cholesterol and develop progressive atherosclerosis. The present investigation was undertaken to evaluate the vascular responses to vasoactive compounds of aorta from WHHL rabbits and normal New Zealand White (NZW) rabbits at 1 and 6 months of age. Rings of distal thoracic aorta were suspended under isometric tension in oxygenated Krebs buffer. Developed tension was measured in response to graded concentrations of agonists. Maximal responses to KCl (40 mM) were the same in aortas from the 1-month-old and 6-month-old WHHL and NZW rabbits. Aortas from 1-month-old animals were more sensitive to serotonin than aortas from 6-month-old animals. Aortas from WHHL rabbits exhibited an increased maximal response to serotonin when compared with NZW controls. In contrast, the constrictor responses to norepinephrine were reduced in WHHL rabbits compared with NZW rabbits at both age groups. Methacholine decreased tension development in serotonin-contracted vessels. This relaxation was greatest in aortas from NZW rabbits. In 1-month-old NZW rabbits fed a high cholesterol diet, the constrictor responses to serotonin and the relaxation responses to methacholine did not differ from NZW rabbits ingesting a normal diet. However, the responses to norepinephrine were markedly attenuated in the hypercholesterolemic NZW rabbits. Microscopic evaluation of the aortas revealed occasional adherent leukocytes and irregularities in the vascular endothelium in 1-month-old WHHL animals. These changes were greater in aortas from 6-month-old WHHL animals, with more adherent leukocytes, adherent platelets, and severe irregularities in the endothelial surface.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Augmented vasoconstrictor responses to serotonin precede development of atherosclerosis in aorta of WHHL rabbit. 264 71


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