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

We examined the correlation between elastolysis and abnormal accumulation of microfibrils in the arteries of rabbits using light and electron microscopic and tissue culture techniques. Partial constriction of the common carotid arteries of rabbits gave rise to gradual atrophy of the media with elastolysis and an unusual accumulation of microfibrils. With advancing experimental atherosclerosis in cholesterol-fed rabbits, the elastofibrotic intima generally became thick and hyalinized and was replaced by bundles of microfibrils lacking elastin or associated with only tiny elastin aggregates and disrupted elastic fibers. Organ cultures of aortic explants from rabbits with or without pancreatic elastase supplementation for 5 days disclosed that there was complete loss of medial elastic fibers and increasing deposition of microfibrils, morphologically identical to elastin-associated microfibrils, around viable smooth muscle cells only in the elastase supplemented group. These observations suggest that abnormal accumulation of microfibrils in the elastic tissue is closely associated with excessive elastolysis of preformed or newly formed elastic fibers during elastic tissue remodeling. Enhanced synthesis of microfibrils may occur in response to elastolysis as a reparative phenomenon.
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PMID:Abnormal accumulation of elastin-associated microfibrils during elastolysis in the arterial wall. 230 10

Atherosclerosis is an arterial disease characterized by focal accumulation of collagen, elastin, lipids, and calcium at sites associated with macrophage infiltration and altered smooth muscle metabolic function. Studies in several types of animal models, especially cholesterol-fed rabbits, have shown that calcium competitors, calcium chelators, anticalcifying agents, and calcium channel blockers can reduce the accumulation of atherogenic lesion components and thus apparently decrease the progression of lesions. Although there are some conflicting data in the animal model studies using calcium channel antagonists, as a result of differences in experimental designs, it is now apparent that several classes of calcium channel blockers inhibit the progression of early arterial lesions induced by cholesterol feeding. The dihydropyridine calcium channel blockers appear to be more potent antiatherosclerotic agents than other classes of calcium channel antagonists. Several mechanisms involving regulation of endothelial cell, smooth muscle cell, and macrophage metabolic functions may be responsible for the calcium channel blocker effects on early lesion progression. For example, recent studies in cell culture model systems suggest that calcium channel blockers may significantly alter activities that regulate lipoprotein-derived cholesterol accumulation by cells. Some of these activities are independent of calcium flux across voltage-operated calcium channels. Thus, calcium channel blockers may reduce the progression of atherogenic lesions by a combination of decreasing calcium accumulation within arterial wall cells and by altering calcium-independent metabolic activities.
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PMID:The antiatherogenic potential of calcium antagonists. 246 1

S-protein/vitronectin is a multifunctional glycoprotein interacting with both complement activation and coagulation pathways. Its presence was investigated in 5 femoral and 5 iliac atherosclerotic human arteries, obtained at surgery, by immunoelectron microscopy using an affinity purified rabbit IgG specific for human S-protein/vitronectin. The immunoelectron dense specific deposits were found in both intimal thickenings and fibrous plaques in association with elastic fibers, collagen bundles and cell debris in the vicinity of elastin. Cell debris embedded in the collagen matrix were S-protein/vitronectin negative. S-protein/vitronectin was also absent on intact cells, lipid droplets and cholesterol clefts. All cell debris, however, was positive for C5b-9 deposits suggesting that complement activation had occurred at these sites with or without S-protein/vitronectin interaction. S-protein/vitronectin may play a role in the arterial wall defence by restricting the extent of complement activation.
Atherosclerosis 1989 Aug
PMID:Immunoelectron-microscopic localization of S-protein/vitronectin in human atherosclerotic wall. 247 93

Aneurysms of the abdominal aorta occur with atherosclerosis or connective tissue disorders. Changes of three components of aortic media, smooth muscle cells, elastin, and collagen, which could contribute to medial weakening, are discussed. Smooth muscle cells cultured from the aging abdominal aorta (normal, atherosclerotic, or aneurysmal) have limited replicative potential at five to six cell doublings, whereas cells from aneurysmal thoracic aorta undergo more than 20 cell doublings in culture. The elastin content is much reduced in aneurysms and this is associated with an increase in elastase activity of medial homogenates to 17.8 U/ng of deoxyribonucleic acid (DNA) compared with 8.3 and 4.4 U/ng of DNA in atherosclerotic and normal aorta, respectively. An elastinolytic enzyme has been purified from aneurysmal aorta and appears to have different properties from human leukocyte elastase. Ruptured aneurysms are associated with an increased total collagenase activity but the increase could be stimulated by, or result from, an influx of inflammatory cells and does not necessarily have a causal significance. In patients with a family history of aneurysm there appears to be a decreased content of type III collagen in aortic media: 24% +/- 4% compared with 32% +/- 5% in most aneurysms. Familial aneurysms are most common in women, and preliminary results suggest that a polymorphic variant of the type III collagen gene, defined by restriction enzyme digest, may be associated with aneurysmal disease in women. The genetic approach may define causal mechanisms predisposing patients to aneurysmal dilatation.
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PMID:Cellular, enzymatic, and genetic factors in the pathogenesis of abdominal aortic aneurysms. 253 34

Atherosclerosis is an arterial disease characterized by localized accumulation of collagen, elastin, lipids, and calcium at sites associated with macrophage infiltration and altered smooth muscle metabolism. Studies in several types of animal models, especially cholesterol-fed rabbits, have shown that calcium competitors, calcium chelators, anticalcifying agents, and calcium antagonists can reduce the accumulation of atherogenic lesion components and decrease the progression of lesions. Although there are some conflicting data in the animal model studies, it is now apparent that several classes of calcium antagonists inhibit the progression of early arterial lesions induced by cholesterol-feeding in animals. The dihydropyridine class of calcium antagonists may be more potent as anti-atherosclerotic agents than the other classes. Mechanisms involving regulation of endothelial cell, smooth muscle cell, and macrophage metabolism may be responsible for the effects of calcium antagonists on early lesion progression. Recent studies in cell culture-model systems suggest that calcium antagonists may significantly alter activities that regulate lipoprotein-derived cholesterol accumulation by arterial wall cells. Some of these activities are independent of calcium flux across voltage-operated calcium channels. Thus, calcium antagonists may reduce the progression of atherogenic lesions by a combination of decreasing calcium accumulation within arterial wall cells and by altering calcium channel-independent metabolic activities, which affect lesion development.
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PMID:Antiatherogenic properties of calcium antagonists. State of the art. 265 28

The in vivo detection of early atherosclerosis remains a problem. First, atherogenesis is a process with an insidious onset and course. Once clinical signs and symptoms have developed the lesion usually is in an advanced stage. Second, the detection of early atherosclerotic lesions creates the problem of distinguishing between almost natural, age-related intimal changes and intimal thickening as a precursor lesion of atherosclerosis. The hallmark of atherosclerosis is the abnormal deposition of lipids within the intima. This process is accompanied by a cellular response, composed of macrophages, lymphocytes and proliferating vascular smooth muscle cells. An increasing quantity of collagen and elastin fibers eventually will replace the cellular constituents. In other words, a changing histological picture with respect to component make up in time. Third, an adequate interpretation of intimal thickening may be complicated further by tissue characteristics of the arterial media. The elastin units of an elastic type artery produce an echo-dense image, whereas a muscular media is hypoechoic. All in all it seems fair to state that ultrasound imaging techniques, at least for the time being, will be inadequate to distinguish between 'early' atherosclerotic lesions and intimal thickenings which will not necessarily progress to the full blown lesion.
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PMID:Ultrasound imaging and atherogenesis. 267 Nov 73

The changes of the intima during subendothelial edema formation were studied by ultrastructural and immunohistochemical methods in the ductus arteriosus (DA) of the dog. Subendothelial edema formation is the first stage in the development of intimal cushions in the DA. Development of intimal cushions is a physiological process preceding normal spontaneous closure after birth. The material consisted of normal canine DA and DA from a strain of dogs with hereditary persistence of the DA (PDA). In the normal DA intimal thickening starts with separation of the endothelial cells from the internal elastic lamina by a widened subendothelial region (SR). Initially this SR is, at the ultrastructural level, composed of granular and amorphous material. Collagen fibrils and elastin are not detected. During the formation of the SR a shedding of the basal lamina underneath the endothelial cells is observed. In the PDA the endothelial cells remain attached to the internal elastic lamina. The topography of the extracellular matrix components collagen type I, III, IV, fibronectin and laminin were studied immunohistochemically. These are important factors in the adherence of the endothelial cells to the underlying intimal layers. Laminin and collagen type I are diffusely present before but absent after detachment of the endothelial cells. Collagen type III, barely detectable before detachment, becomes visible underneath the detached cells. No changes are observed in the distribution of collagen type IV and fibronectin. Comparison of the normal DA with the various types of the PDA strain and controls allowed the conclusion that the observed changes in the extracellular matrix components were confined to those parts of the vessel wall that showed development of intimal thickening. The observed alterations both at the ultrastructural and immunohistochemical level do not explain the initiation of the process of endothelial cell detachment, which have been shown in a previous study to be related to an increase in hyaluronic acid.
Atherosclerosis 1989 Sep
PMID:Ultrastructural and immunohistochemical changes of the extracellular matrix during intimal cushion formation in the ductus arteriosus of the dog. 280 44

Primary cultures of typical and modified smooth muscle cells isolated from the intima of human aorta were used to study the mechanism whereby low density lipoprotein (LDL) induces accumulation of intracellular cholesterol. Incubation of intimal cells with native LDL obtained from human plasma did not lead to deposition of total cholesterol. LDL added to the cultures simultaneously with hyaluronic acid, heparin, chondroitin sulfate, fibronectin, and mouse monoclonal antibody against LDL also failed to alter the cellular cholesterol. On the other hand, 24-h incubation of the cells with LDL in the presence of dextran sulfate, gelatin, particles of aortic elastin, particles of collagenase-resistant aortic matrix, goat polyclonal antibodies against LDL or latex beads caused a significant (1.5-7-fold) increase in total cholesterol. The compounds which stimulated cholesterol deposition are able to form precipitating complexes with LDL. On the contrary, the agents which failed to induce cholesterol accumulation were unable to insolubilize LDL. A direct correlation (r = 0.927) was found between the cholesterol content of the insoluble complex and the increment of cholesterol in the cultured cells. To find out whether LDL plays a specific role in the deposition of intracellular cholesterol, very low density lipoproteins and high density lipoproteins were used. These lipoproteins stimulated the accumulation of intracellular cholesterol in the presence of agents capable of forming insoluble associates with them. Our data suggest that insolubilization of lipoproteins is a key event in the LDL-mediated accumulation of intracellular cholesterol induced by various agents.
Atherosclerosis 1989 Sep
PMID:Insolubilization of low density lipoprotein induces cholesterol accumulation in cultured subendothelial cells of human aorta. 280 47

Arteriovenous fistulae between the external jugular vein and the common carotid artery were surgically fashioned in eight sheep. The altered hemodynamics produced morphological changes similar to those observed in human atherosclerosis. The elastica is a major mural component and undergoes considerable structural variation during lesion development. The most significant biochemical changes in the elastin occur in the experimental vein region. These include a quantitative loss particularly in the midregion of the vein and a decrease in the concentration of up to 20% of the crosslinks (desmosine and isodesmosine). There is an increase in the cholesterol content of the elastin purified from both experimental artery and vein. The bound phospholipid was higher in the experimental artery and in the dilated experimental vein. There was a significant time-dependent loss of elastin in the stressed venous tissue.
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PMID:The biochemical composition of hemodynamically stressed vascular tissue: the insoluble elastin of experimental arteriovenous fistulae. 280 66

Auto-antibodies such as anti-elastin, anti-collagen, anti-nuclear and anti-arterial, circulating immune complexes, and cellular responses to collagen I and III are known to be present in Buerger's disease (EO). Deposits of IgG, C3 and C4 have also been found in the vascular lesions of endarteritis obliterans (EO) in young men. The purpose of this study was to correlate clinical evidence of vascular disease with the presence of the circulating immune complexes. Thirty-three patients suffering from Buerger's disease (EO), 20 patients suffering from atherosclerosis (AT) and 20 normal controls (Norm) were studied. All were male, heavy smokers, and age-matched. Five techniques were used: direct nephelometry, nephelometry with protamine, two polyethyleneglycol precipitation methods (PegIgG and PegC4), and an immuno-enzymatic C1q fixation test (C1qE). The results seem to confirm the presence of circulating immune complexes in peripheral arterial disease in young men who are heavy smokers, particularly those suffering from EO.
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PMID:Circulating immune complexes in Buerger's disease. Endarteritis obliterans in young men. 280 5


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