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

The structural development of the already well defined fetal rabbit aortic wall from 22 to 31 days of gestation in vivo consists of increasing aortic wall thickness, elastic lamina continuities, extracellular matrix deposition, and maturing of the fine structure of the medial smooth muscle cells. In vivo at term (31 days), the mature aortic smooth muscle cells demonstrated the characteristic thin, thick and intermediate filaments, dense plaques, endoplasmic reticulum, golgi, plasmalemma vesicles and an incomplete basal lamina. The fetal aorta rapidly responded to organ culture with various changes. Fetal smooth muscle cells modified their phenotype to the synthetic state when cultured in both serum-supplemented and serum-free media. This smooth muscle cell modification occurred after 3 days of culture in fetal explants. The synthetic type smooth muscle cells (fetal) began to proliferate after 6 days of culture. This proliferation resulted in a peripheral outgrowth after 9 days of 10-20 layers in fetal cultures from serum-supplemented media and of 2-4 layers in serum-free media. The orderly arrangement of the internal elastic lamina and alternating medial layers of smooth muscle cells and elastic lamina seen in vivo was disrupted along with increased matrix after 9 days of fetal explant culture. Significant numbers of 'modified' synthetic phenotype smooth muscle cells were not observed in adult aortic explants until after 15 days in culture in serum supplemented media. The mature contractile phenotype smooth muscle cell predominated in adult explants cultured in serum-free media. Significant synthetic phenotype smooth muscle cell proliferation only occurred in adult explants after 15 days culture in serum-supplemented media. When compared to aorta in vivo evidence for increases in cholesterol esterification were observed in both fetal (9 days) and adult (15 days) explants cultured in both serum-supplemented and serum-free media. The fetal aorta in organ culture appeared to be more susceptible than the adult aorta to (a) phenotypic modulation of smooth muscle cells to the synthetic state, (b) smooth muscle cell proliferation, and (c) early cholesteryl ester accumulation.
Atherosclerosis 1987 Sep
PMID:Studies on aorta during development. I. Fetal rabbit aorta under ex vivo and in vitro conditions: rapid changes in smooth muscle cell phenotype, cell proliferation and cholesterol content with organ culture. 367 6

Homogenates of control and diet-induced atherosclerotic aortas of rabbit were prepared and the levels of DNA, protein, free and esterified cholesterol, and six enzymes known to be associated with various subcellular organelles [N-acetyl-beta-glucosaminidase, beta-galactosidase (lysosomes); cytochrome oxidase (mitochondria); neutral alpha-glucosidase (endoplasmic reticulum); 5'-nucleotidase (plasma membrane); catalase (peroxisomes)] were compared between control and atherosclerotic preparations. The levels of prostaglandins I2, E2, and F2 alpha, based on DNA, also were measured by radioimmunoassay. Atherosclerotic aortas were significantly enriched in catalase activity (440%) and in each of the acid hydrolases (395 and 630%), based on DNA, as well as in free (630%) and esterified cholesterol (930%), based on tissue wet weight, compared to control aortas. The control level of prostaglandin I2 was 10-fold higher than that of prostaglandin E2, which was 3-fold higher than that of prostaglandin F 2 alpha. Prostaglandin I2 doubled in amount with advanced atherosclerosis, while prostaglandin E2 increased over 10-fold, resulting in twice the amount of prostaglandin I2 than E2 in advanced atherosclerosis; the level of prostaglandin F2 alpha did not appear to change significantly with atherosclerosis. Increased levels of prostaglandins I2 and E2 were correlated significantly with increased aortic total cholesterol content (based on DNA) but not increased serum cholesterol levels. N-Acetyl-beta-glucosaminidase activity also was correlated significantly to aortic total cholesterol content and beta-galactosidase activity, as well as to the level of prostaglandin I2; in contrast, N-acetyl-beta-glucosaminidase was not significantly correlated to prostaglandin E2. The association of prostaglandins I2 and E2 with aortic total cholesterol suggests the participation of prostaglandins in the response of arterial cells to lipid accumulation in atherosclerosis. The specific association of aortic prostaglandin I2 level and N-acetyl-beta-glucosaminidase activity further suggests a possible role for this prostaglandin during arterial intralysosomal cholesterol accumulation.
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PMID:Arterial prostaglandins and lysosomal function during atherogenesis. I. Homogenates of diet-induced atherosclerotic aortas of rabbit. 389 3

Smooth muscle cells were isolated enzymatically from adult human arteries, grown in primary culture in medium containing 10% whole blood serum, and studied by transmission electron microscopy and [3H]thymidine autoradiography. In the intact arterial wall and directly after isolation, each smooth muscle cell had a nucleus with a wide peripheral zone of condensed chromatin and a cytoplasm dominated by myofilament bundles with associated dense bodies. After 1-2 days of culture, the cells had attached to the substrate and started to spread out. At the same time, a characteristic fine-structural modification took place. It included nuclear enlargement, dispersion of the chromatin and formation of large nucleoli. Moreover, myofilament bundles disappeared and an extensive rough endoplasmic reticulum and a large Golgi complex were organized in the cytoplasm. This morphological transformation of the cells was completed in 3-4 days. It was accompanied by initiation of DNA replication and mitosis. The observations demonstrate that adult human arterial smooth muscle cells, when cultivated in vitro, pass through a phenotypic modulation of the same type as arterial smooth muscle cells from experimental animals. This modulation gives the cells morphological and functional properties resembling those of the modified smooth muscle cells found in fibroproliferative lesions of atherosclerosis. Further studies of the regulation of smooth muscle phenotype and growth may provide important clues for a better understanding of the pathogenesis of atherosclerosis.
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PMID:Adult human arterial smooth muscle cells in primary culture. Modulation from contractile to synthetic phenotype. 396 87

Aortic intima-medias of normal and cholesterol-fed rabbits were studied with EM and cells were isolated by enzyme digestion. The composition of cytoskeletal and cytocontractile proteins was determined with SDS-PAGE and the primary growth and thymidine incorporation rates were assessed after seeding the cells into tissue culture flasks. Ultrastructurally, the SMCs in the thickened atherosclerotic intima differed from the contractile medial SMCs in containing lipid vacuoles, enlarged endoplasmic reticulum and a reduced number of myofilaments, thus showing characteristics of dedifferentiated SMCs. In SDS-PAGE, freshly isolated cells from the atherosclerotic intima-medias had a lower content of myosin and actin, and a higher proportion of vimentin and desmin than SMCs from normal aortas. Enzyme-isolated SMCs from normal aortas did not start to grow and incorporate radioactive thymidine until 5-6 days after seeding, whereas those from atherosclerotic aortas did so within 2 days. After a week in culture, SMCs from both sources resembled each other, and had decreased contents of myosin and actin, and increased concentrations of vimentin in comparison to freshly isolated normal SMCs. The present results indicate (a) that morphological dedifferentiation of SMCs in aortic lesions of cholesterol-fed rabbits is associated with an increased proportion of the proteins of the intermediate filaments and a decrease in those of the thin and thick myofilaments as determined with SDS-PAGE, and (b) that similar changes take place when normal SMCs are cultured in vitro. The results also suggest (c) that enzyme-isolated atherosclerotic SMCs proliferate in a primary culture without the lag period that normal SMCs apparently require for dedifferentiation.
Atherosclerosis 1984 Jul
PMID:Growth properties and composition of cytoskeletal and cytocontractile proteins in aortic cells isolated and cultured from normal and atherosclerotic rabbits. 646 13

The effects of long-term gemfibrozil (Lopid) therapy on human liver structure are not known. Studies of this nature are becoming essential in determining the risk/benefit ratio since gemfibrozil is an effective agent for the control of hyperlipoproteinemia types IIa, IIb, and IV. Particularly, gemfibrozil is effective when dietary management or available therapeutic control fail to reduce serum cholesterol and triglycerides as well as normalizing the lipoprotein pattern. Percutaneous liver biopsies of 9 patients on long-term gemfibrozil therapy were evaluated by light microscopy, interference contrast optics and transmission electron microscopy. The distribution of patients according to lipoprotein phenotype was 3 Type IIa, 3 Type IIb, and 3 Type IV. Their lipoprotein patterns approached normal and the serum lipids were controlled during gemfibrozil therapy. By light microscopy, the lobular architecture and other parameters were within normal limits. Varying degrees of fatty change were found as would be expected. No preferential lobular disposition of the fat globules was evident. Coalescence of fat droplets, nuclear displacement and fatty cysts were noted. Differential interference contrast microscopy revealed several degrees of contrast amplitude in these droplets suggesting a heterogeneous lipid deposition in hepatocytes. The subcellular analysis revealed a moderate degree of glycogen deposition, absence of nuclear abnormalities and unremarkable mitochondria; the rough endoplasmic reticulum was not significantly altered and smooth surfaced membranes appeared proliferated. Detailed analysis of the peroxisome population showed matrix rarefaction, marginal plate formation and spurious densities though no significant proliferation occurred. Distribution of peroxisomes in hepatocytes varied widely from cell to cell and in different lobular areas. This study confirmed the association of hepatic fatty change with hyperlipoproteinemia irrespective of the pattern observed in circulating lipoproteins. Peroxisome proliferation, as seen in rodents when receiving gemfibrozil, did not occur and the structure of these subcellular organelles was not compromised. It was concluded that the long-term administration of this compound did not show adverse effects on the hepatocyte in hyperlipoproteinemia.
Atherosclerosis 1982 May
PMID:Light and electron microscopy of liver in hyperlipoproteinemic patients under long-term gemfibrozil treatment. 680 26

The administration of lipid-lowering drugs to rodents, notably those related to clofibrate, rapidly provokes a hepatic response characterized by hepatomegaly, proliferation of smooth endoplasmic reticulum and proliferation of peroxisomes in hepatocytes. In some studies hepatocellular carcinoma has been found in rats or mice exposed for their entire life-span to high dose levels of various fibrates. In the present study liver biopsy samples were obtained from 38 hyperlipidemic patients, 28 of whom had been receiving fenofibrate for between 2 months and approximately 3 years (mean values: males 1.79, females 1.98 years). The remaining 10 patients had never been treated with a lipid-lowering drug. Examination of the biopsy samples by a variety of optical techniques and by electron microscopy failed to reveal any difference between the groups. Peroxisomes were relatively rare, there being no evidence of the clear proliferation seen in rodent studies. Other microscopic features of interest were some variation of nuclear size, mitochondria containing paracrystalline inclusions, dilated endoplasmic reticulum associated with reduced amounts of rough endoplasmic reticulum, and the presence of lipid droplets in the liver cells. However, these variations from normal were in general not much more apparent in samples from the fenofibrate-treated patients than in the untreated group. Light- and electron-microscopic observations did not suggest liver intoxication or a carcinogenic pattern.
Atherosclerosis 1983 Jan
PMID:Influence of fenofibrate on cellular and subcellular liver structure in hyperlipidemic patients. 683 87

Isolated smooth muscle cells from the adult pig and rabbit aorta in primary culture undergo a spontaneous change in phenotype from a contractile to a synthetic state over 6-8 days, losing their capacity to contract and gaining the capacity to divide. The change in smooth muscle phenotype to the synthetic state is accompanied by distinct changes in the cells' ability to metabolize LDL, with the rate of degradation of 125I-labelled LDL decreasing to about one fifth of the level in contractile state cells. This does not appear to be due to changes in the number or affinity of LDL receptors since saturable binding of LDL is unaltered. The specific activities of the lysosomal enzymes acid phosphatase and N-acetyl-beta-glucosaminidase increase with change to the synthetic state as do cytochrome c oxidase (mitochondria) and NADPH-dependent cytochrome c reductase (endoplasmic reticulum). In contrast there is a slight but not significant decrease in the specific activity of the lysosomal enzyme acid cholesteryl esterase of rabbit smooth muscle cells and a significant decrease in the activity of pig cells with change in phenotype to the synthetic state. Significantly more [3H]cholesteryl oleate is recovered in synthetic state than in contractile state cells following incubation with 20 micrograms/ml unlabelled LDL and [3H]sodium oleate. Morphologically there is no difference in the number of lipid droplets in contractile and synthetic state cells after incubation in 5% normolipemic serum, but in cells grown in 10% hyperlipemic serum for 4 days synthetic state cells become almost completely filled with lipid droplets while contractile state cells are unaffected. Lipid accumulation also occurs selectively in vivo in synthetic as compared with contractile state smooth muscle cells within intimal fibromuscular thickenings induced by de-endothelialization of the carotid artery of cholesterol-fed rabbits. We suggest that accumulation of lipid in smooth muscle cells of atherosclerotic plaques is related to reduced catabolism of LDL following smooth muscle phenotypic change from the contractile to synthetic state.
Atherosclerosis 1983 Jun
PMID:Lipid accumulation in arterial smooth muscle cells. Influence of phenotype. 688 1

We studied the ultrastructure of the left anterior descending coronary artery in 6 female cynomolgus macaques fed atherogenic food containing 0.5% cholesterol for 6 months, and in 2 female cynomolgus macaques that had received food low in cholesterol. Animals given the atherogenic food had coronary artery lesions of a characteristic two-level architecture consisting of a lipid-poor upper cap, and of a lipid-rich lower core. The cap consisted of layers of smooth muscle cells that were rich in rough endoplasmic reticulum and contained few myofilaments and relatively few lipid droplet inclusions. The core consisted mainly of macrophages overloaded with droplet inclusions (macrophage foam cells), droplet-laden smooth muscle cells, and extracellular lipid and cell debris. Some macrophage foam cells were in mitosis. The largest lipid cores contained multinucleate giant cells with large intracellular crystal clefts. Dead macrophage foam cells were the source of the extracellular lipid and debris particles. Intimal cores often extended into the adjacent media. The adventitia was involved in the intima-media lesions in 3 of the animals. Compared with the coronary artery lesions of rhesus macaques and patas monkeys given similar atherogenic diets, cynomolgus monkey lesions were morphologically closer to human atherosclerotic plaques with respect to their stratification into a cap and a core.
Atherosclerosis 1982 Jun
PMID:Ultrastructure of experimental coronary artery atherosclerosis in cynomolgus macaques. A comparison with the lesions of other primates. 711 59

Degenerative changes in endothelial and smooth muscle cells from fetal, 2-month-, and 6-month-old swine ductus vasculature were observed. In fetal ductus, a discontinuous internal elastic lamina and increased extracellular mucopolysaccharide deposition were initially noted. At 2 months of age, there was widespread fibromuscular intimal thickening, the appearance of modified smooth muscle cells, increased medial fibrosis, and the occurrence of cell debris and nuclear pyknosis. Early modification of smooth muscle cells was marked by increased occurrence of lysosomes, widely dilated rough endoplasmic reticulum, and Golgi bodies. Abundant aggregates of Weibel-Palade bodies occurred in early endothelial cell degeneration. At 6 months of age, after complete anatomical closure, there was abundant lipid vacuole production by degenerated medial smooth muscle cells. This study demonstrates that at various stages of occlusion, endothelial and smooth muscle cells from ductus vasculature exhibit morphological changes which are qualitatively similar to atherosclerosis.
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PMID:Degenerative changes in endothelial and smooth muscle cells from aging swine ductus arteriosus and venosus. 721 15

The formation and growth of atherosclerotic lesions in experimental hypercholesterolemia has been attributed to endothelial injury. Many injured endothelial cells have been observed in the periphery of the lesions, but few in the central parts. In the present study, we have investigated the distribution of endothelial cells, leucocytes, and smooth muscle cells on the surface of the lesions, as well as the regeneration of the surface cell layer, on dietary induced experimental atherosclerotic lesions. In central areas of the lesions, flat cells with Weibel-Palade bodies and intercellular junctions characteristic of endothelium, were observed on the surface. In peripheral areas of the lesions, surface cells were more bulging and contained many free ribosomes and short cisternae of endoplasmic reticulum, suggesting that these cells were more primitive. Weibel-Palade bodies and typical intercellular junctions suggested that many of the cells should be regarded as endothelial cells. ANAE- positive monocytes were also frequent in these areas. The incorporation of 3H-thymidine was considerably larger over the lesions than in the surrounding normal tissue, suggesting a regeneration of the endothelial cell layer from cells on the lesions. Still regression does not occur after re-endothelialization in dietary induced atherosclerosis. This contrasts with the development of lesions induced by mechanical injury, and may be of importance for understanding the role of hypercholesterolemia in atherogenesis.
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PMID:Endothelial proliferation and atherogenesis in rabbits with moderate hypercholesterolemia. 721 20


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