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

This review summarizes progress in nonenzymatic glycosylation research of potential relevance to atherosclerosis using a hypothetical model based on current concepts of atherogenesis. Recently, new information has been presented showing that the initial Amadori product undergoes a series of further reactions and rearrangements to form adducts, called advanced glycosylation end products (AGE). These products are irreversible and accumulate indefinitely on long-lived molecules. These AGE covalently trap soluble plasma proteins, act as signals for macrophage recognition and uptake, and induce mutations in double-stranded plasmid DNA. Covalent trapping of low-density lipoprotein (LDL) by AGE on collagen or elastin could promote lipid accumulation in the arterial wall, whereas AGE trapping of von Willebrand factor would increase platelet adhesion and aggregation leading to intimal smooth muscle cell proliferation. Recognition and uptake of AGE-proteins by scavenging macrophages could further contribute to the process of atherogenesis by stimulating release of macrophage secretory products such as macrophage-derived growth factor. Accumulation of AGE on smooth muscle cell DNA might also enhance arterial smooth muscle cell proliferation by increasing the rate of mutations affecting growth controls. This model should provide the basis for future experiments.
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PMID:Role of nonenzymatic glycosylation in atherogenesis. 351 22

The aortic walls of patients with abdominal aortic aneurysms (AAA) and of healthy controls were examined for elastin, collagen I and III, and the intermediate filament proteins desmin and vimentin by immunohistochemical, enzyme histochemical, and routine histological techniques. The morphology of the aneurysmatic walls varied considerably from case to case, but many pathological changes were seen in all cases, e.g., extensive atherosclerotic plaques in the intima, prominent alterations in amount and organization of the elastic lamellae in the media, and an increase of connective tissue. Both collagen I and III were present in all the aneurysmatic walls. The smooth muscle cells in all the aortic walls showed a marked heterogeneity with respect to the morphological appearance, the enzyme histochemical features, and the content of desmin and vimentin. Vimentin occurred in some intimal, medial muscle, and adventitial cells of both the controls and the AAA patients. Desmin occurred in some of the intimal, medial, and adventitial muscle cells of both the controls and the AAA patients. All the cells with desmin in the intima and media also contained vimentin. Thus, smooth muscle cells in the walls of both the normal human abdominal aorta and aneurysms contained either vimentin, desmin, or both. This variability may be explained by the presence of different phenotypes of smooth muscle cells and could be of significance for the development of atherosclerosis and aneurysms. Of special interest was the finding that 5 of the 24 AAA patients studied had blood relatives with the same disease, suggesting a hereditary influence. However, no systematic differences between the morphological appearance of the aneurysmatic walls in familial and nonfamilial AAA could be detected.
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PMID:Abdominal aortic aneurysms: distribution of elastin, collagen I and III, and intermediate filament proteins desmin and vimentin--a comparison of familial and nonfamilial aneurysms. 353 8

The events involved in atherogenesis include platelet deposition on damaged endothelial surfaces; migration and proliferation of smooth muscle cells; the formation of elastin, collagen, and glycosaminoglycans, followed by the penetration and complexing of lipoproteins; and, calcification. Since calcium is involved in these and other events, considerable data exist on the effects of altering calcium influx in experimental atherosclerosis. Interventions that increase calcium deposition tend to increase the severity of experimental atherosclerosis, whereas interventions that reduce calcium entry into cells tend to reduce its progression. Using rabbits, researchers have recently focused on the ability of calcium channel blockers, such as nifedipine, verapamil, and diltiazem, to attenuate the development of experimental atherosclerosis. Studies also suggest that although calcium channel blockers may protect against the development of experimental atherosclerosis, they are less effective in inducing its regression. Further, studies with calcium channel blockers in rabbits deficient in low-density lipoprotein receptors did not show protection against the development of atherosclerosis. However, no clinical studies are yet available to judge the potential protective effects of calcium channel blockers in humans. Since many patients are now receiving long-term calcium blocker therapy for hypertension, these findings may be relevant in the selection of antihypertensive therapy, provided that protective effects can be demonstrated.
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PMID:Calcium channel blockers and atherogenesis. 355 1

Abnormal accumulation of connective tissue in blood vessels contributes to alterations in vascular physiology associated with disease states such as hypertension and atherosclerosis. Elastin synthesis was studied in blood vessels from newborn calves with severe pulmonary hypertension induced by alveolar hypoxia in order to investigate the cellular stimuli that elicit changes in pulmonary arterial connective tissue production. A two- to fourfold increase in elastin production was observed in pulmonary artery tissue and medial smooth muscle cells from hypertensive calves. This stimulation of elastin production was accompanied by a corresponding increase in elastin messenger RNA consistent with regulation at the transcriptional level. Conditioned serum harvested from cultures of pulmonary artery smooth muscle cells isolated from hypertensive animals contained one or more low molecular weight elastogenic factors that stimulated the production of elastin in both fibroblasts and smooth muscle cells and altered the chemotactic responsiveness of fibroblasts to elastin peptides. These results suggest that connective tissue changes in the pulmonary vasculature in response to pulmonary hypertension are orchestrated by the medial smooth muscle cell through the generation of specific differentiation factors that alter both the secretory phenotype and responsive properties of surrounding cells.
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PMID:Smooth muscle-mediated connective tissue remodeling in pulmonary hypertension. 360 30

The histological, ultrastructural, morphometrical and histochemical aspects of the arterial media were studied in young and aged SHR, and compared to normotensive Wistar Kyoto rats. The diffuse thickening was the most characteristic feature of the hypertensive media. It seems due to three processes: Early generalized hypertrophy of smooth muscle cells (smc); connective matrix neogenesis and smc proliferation, more evident in peripheral vasculature. The present paper discusses the following hypertensive tunica media changes in relation to the atherosclerotic process: the decrease in lipolytic esterase and cholinesterase activities; the activation of some lysosomal enzymes; the increase in collagen, glycosaminoglycan and elastin content; the increased media thickness; the modified smc behavior (migration, secretion, proliferation). These alterations might positively influence arterial susceptibility to atherosclerosis through reduced smc lipolytic activity; slowed transmural diffusion; perturbed efflux and aggravated media hypoxia.
Atherosclerosis 1987 May
PMID:Tunica media changes in the spontaneously hypertensive rat (SHR). 360 28

The level of the circulating elastin-derived peptides (CEDP) in the serum is believed to reflect the activity of the degradation of the elastic structures. This paper reports a new method, based on the 'sandwich' version of the enzyme-linked immunosorbent assay (ELISA), for the detection and quantification of CEDP in human serum. By this method we investigated the age-related changes in their level among healthy subjects within the age range of 1 and 75 years and among atherosclerotic subjects aged 50 to 75 years. The highest level of CEDP was found in the serum of the atherosclerotic patients, and the lowest, among the healthy subjects between 18 and 50 years of age.
Atherosclerosis 1987 Jul
PMID:Age-related changes in the level of circulating elastin-derived peptides in serum from normal and atherosclerotic subjects. 363 48

To elucidate the nature of the abnormality of elastin metabolism in arteriosclerosis, we determined the elastase-type activity in the human radial artery of patients with chronic renal failure due to glomerular disease and diabetes. Elastase-type activity was determined by HPLC analysis of the hydrolyzed products of succinyl-trialanine-4-nitroanilide, a sensitive synthetic substrate for elastase. Three kinds of hydrolyzed products, (L-Ala)2-NA, L-Ala-NA and NA, were found after incubation of the substrate with human radial artery in the presence of amastatin (an inhibitor of aminopeptidases). We assumed the activity that liberates NA to be an elastase-type activity because purified human aorta elastase liberates NA from the substrate. The pH optima of the human artery and rat aorta activities were 6.0 and 6.8, respectively. The elastase activity in human radial artery and rat aorta was inhibited by diisopropyl phosphofluoridate, a serine protease inhibitor, and by elastatinal, an elastase inhibitor. The elastase-type activity in the radial artery of patients with chronic renal failure was significantly lower than that of the control group, and the decrease was especially marked in the patients with juvenile onset diabetes. These results suggest that the elastin metabolism is abnormal in the radial artery in diseases that tend to cause atherosclerosis.
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PMID:Elastase-type activity in human radial artery in patients with chronic renal failure. 363 13

The effect of elastin peptides (Kappa-elastin) was investigated on human monocytes. The data presented here indicate that elastin peptides increase the intracellular Ca2+ level measured by Quin 2 fluorescence and mediate the release of beta glucuronidase and elastase. The O2 consumption and H2O2 release were stimulated in a dose-dependent manner. The early rise of cAMP was followed by a return to the original level at 30 min and by a concomitant increase of cGMP level. The action of elastin peptides on intracellular calcium level and cGMP levels may well be related to its previously demonstrated chemotactic activity. These activities may well play a role in the modifications of the extracellular matrix following elastin degradation as observed in atherosclerosis, emphysema and aging.
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PMID:Effect of elastin peptides on human monocytes: Ca2+ mobilization, stimulation of respiratory burst and enzyme secretion. 364 24

Elastase has been reported to have a multiplicity of activities which may be protective against atherosclerosis. The data reported here support those reports and show a clear antiatherosclerotic effect in hyperlipidemic chickens. We have shown here that a reduction in calcium and lipid accumulation in aortic tissue and possibly a plasma cholesterol lowering effect can be seen in the chicken when treated with elastase. The most important effect in this animal is probably to aid removal of lipid bound to elastin in the intima. This was achieved at a dose of only 600 U elastase while reductions in tissue calcium required 1800 U elastase.
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PMID:The effect of elastase on chickens with endogenous hyperlipidemia. 364 61

Histological sections through the walls of abdominal aortic aneurysms showed scarce and disrupted elastic tissue. The elastin content of the aneurysmal aortic media was only 8.1 +/- 3.2% dry defatted weight (n = 11). The elastin content of grossly normal age and anatomically matched aortic media was 35.0 +/- 3.2% dry weight (n = 4) and the elastin content of severely atherosclerotic, stenosed infrarenal aortic media was 22.0 +/- 7.2% dry weight (n = 6). There was an inverse correlation of elastin content with the elastinolytic activity of aortic media homogenates, r = -0.78. Elastase activity, measured by the hydrolysis of [3H]elastin, was highest in aneurysmal aortic homogenates, 92.1 +/- 43.7 U/mg protein (n = 18), falling to 46.9 +/- 13.3 U/mg protein (n = 13) in severely stenosed atherosclerotic aortic homogenates and 35.5 +/- 11.9 U/mg (n = 6) in grossly normal aortic homogenates. The elastinolytic activity of stenotic aorta contained leukocyte elastase as an important component. In aneurysmal homogenates leukocyte elastase was also found but the increased elastase activity resulted from a protease(s) (Mr 95,000) extracted in 2 M urea, having minimal specificity for alanyl bonds and no immunological cross-reactivity with leukocyte elastase.
Atherosclerosis 1987 May
PMID:Elastin degradation in abdominal aortic aneurysms. 364 36


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