Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polar coordinate mapping was used to determine the rate of growth of individual sudanophilic lesions on the aortic wall around several major branches of the aortae of cholesterol fed rabbits. Four groups, with 6 8-month old male albino white rabbits in each, were used in the study. One group served as a control and the remaining 3 were fed a diet of 2% cholesterol and 6% heated corn oil mixed with ground rabbit pellets for 4, 8, and 10 weeks each. Animals were sacrificed, the aortae removed, stained with Sudan III, pinned at in vivo dimensions, and mapped by the polar coordinate method. No sudanophilic lesions were observed in the control animals. In the experimental groups, the early lesions, except the coronaries, were almost entirely distal to the orifices, and maintained roughly the same contour while spreading around the orifice. The coronary lesions completely encircled the orifices as described previously. As lesions progressed, they became elevated and often granular, so that the lesions themselves may have affected flow profiles around the orifices. Lesions around adjacent orifices were fused in 48% of the cases after 10 weeks on the diet, as opposed to 2% after 4 weeks on the diet. More prolonged experiments were not possible with this diet as the animals developed jaundice and diarrhea. Hemodynamically, these results suggest that early sudanophilic lesions in cholesterol-fed rabbits develop on the aortic wall in areas of high shear stress.
Atherosclerosis 1976 Oct
PMID:The effect of the duration of cholesterol feeding on the development of sudanophilic lesions in the rabbit aorta. 6 80

Atherosclerotic lesions are characterized by lipid infiltration in regions with high rates of endothelial cell turnover. The present investigation was designed to elucidate the route of macromolecular transport across vascular endothelium. The aorta and vena cava of male Sprague-Dawley rats were perfusion-fixed after the intravenous injection of Evans-blue albumin (EBA) or horseradish peroxidase (HRP). Fluorescence microscopic examination of en face preparation of the aorta stained with hematoxylin allowed the identification of endothelial cells that underwent mitosis, together with the localization and quantification of fluorescent spots for EBA leakage. The HRP specimens were subjected to histochemical treatment, and HRP leakage was seen as brown spots under the light microscope. Silver nitrate stain was added in both EBA and HRP studies to outline cell boundaries and to visualize stigmata, stomata, and dead cells. In the aorta, almost every dividing cell showed junctional leakage to albumin and HRP, with clustering of leaky spots around the branch orifices. Time-dependent studies showed gradual increases in the diameter and number of these heterogeneously sized leaky spots, which finally fused to sizes corresponding to the "blue areas" for EBA or "brown areas" for HRP. Compared with arteries, veins had fewer mitotic cells, but more dead cells and diffuse dye-staining areas, indicating a more rapid transport of macromolecules. The leaky spots in the artery were associated mainly with mitotic cells, dead cells, and stigmata, whereas those in the vein occurred primarily at regions with dead cells. These results suggest that the preferential association of the enhanced transport of macromolecules with mitosis in the arterial as compared to venous endothelium and the differential behavior in transmural transport between arteries and veins may form the basis for the predilection of atherosclerosis in arteries.
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PMID:Macromolecular transport across arterial and venous endothelium in rats. Studies with Evans blue-albumin and horseradish peroxidase. 218 Mar 95

Islets of Langerhans in sections from the tail of the pancreas of corpulent LA/N-cp rats and lean controls aged 1, 3, 6 and 9 mo were examined by immunocytochemistry and morphometrically using an automatic image analyzer. The corpulent rats had significantly greater islet volumes at all ages, although islet hypertrophy tended to plateau after 6 mo. By 12 mo age the architecture of the islets was disrupted with large islets fused and showing areas of fibrosis and deposits of hemosiderin. The volume density (v/v, %) of islets in the parenchyma was significantly increased at each age step in corpulent rats reaching over 20% at 9 mo, and was greater in corpulent than in lean rats at all ages. In the corpulent rats, B-cell volume density dramatically with age and at all ages was significantly greater in corpulent than in lean rats. A-cell volume density was significantly greater in the corpulent rats than in lean rats at 1 and 9 mo. The mean B:A cell ratio was greater in corpulent than in lean rats at 3, 6 and 9 mo. There were more D cells per islet in corpulent than in lean rats up to 9 mo. These changes in cell populations were paralleled by qualitative changes in islet morphology and cellular topography such as increasingly irregular islet shape in corpulent animals and by variations in plasma levels of insulin and glucagon. In this strain of rats, obesity is associated with major changes in pancreatic morphology and this correlates strongly with the susceptibility of the strain to atherosclerosis.
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PMID:Age-related qualitative and quantitative changes in the endocrine pancreas of the LA/N-corpulent rat. 332 19

The differences in the fatty acid spectra of serum samples obtained from vegetarians (62 females, 40 males) and non-vegetarians (70 females, 38 males) were evaluated in a matched-pair study design. This study population made it possible to examine 48 female and 31 male pairs whose age difference did not exceed 3 years. The pairs were further matched by education, social status and health-consciousness. The fatty acid pattern of whole serum total lipids and HDL total lipids were determined by GLC. In particular linoleic, linolenic, oleic and docosahexaenoic acid reveal statistically significant differences due to different nutritional habits. A subsample (n = 20) of sera from the 2 groups was investigated by separation of lipid classes by TLC and GLC on a SP 2,340 fused-silica capillary column in order to separate cis-trans fatty acids additionally. This part of the study gives detailed information concerning the fatty acid composition of cholesteryl esters, triglycerides, diglycerides, free fatty acids and phosphatidylcholine. In all those fractions the fatty acid profiles reflect the dietary consumption of lipids. Palmitoleic, vaccenic and docosahexaenoic acid as markers of omnivorous nutrition reach levels of 5, 5 and 3% respectively in non-vegetarians, while they remain remarkably lower in vegetarians. The most prominent difference is the higher amount of linoleic acid in all lipid classes of vegetarian serum samples. The highest amount of trans fatty acids (up to 3%) was detected in di- and triglycerides.
Atherosclerosis 1987 May
PMID:Fatty acid patterns in triglycerides, diglycerides, free fatty acids, cholesteryl esters and phosphatidylcholine in serum from vegetarians and non-vegetarians. 360 30

The capillary gas chromatography of cholesteryl esters after splitless injection into a 25-m, OV-1-coated, fused silica WCOT column and a 7-m Silar 10C-coated glass WCOT column is reported. The nonpolar OV-1 column separated the cholesteryl esters principally on the basis of carbon number, but separation of the saturated esters from the unsaturated esters was also achieved. The polar Silar 10C column separated the esters mainly according to the degree of unsaturation. Thus, the 2 column types complement each other in the analysis of nanogram quantities of cholesteryl esters from small samples, such as those from plasma or single arterial atherosclerosis lesions. This technique therefore obviates some of the difficulties of analyzing such cholesteryl ester samples in the form of methyl esters (incomplete transmethylation, and contamination by solvent impurities and/or plasticizer esters). Both columns were also found to be useful for the separation and quantitation of the t-BDMS ethers of cholesterol and epicholesterol in mixtures containing various proportions of these epimers.
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PMID:Determination of cholesteryl esters and of cholesteryl and epicholesteryl silyl ethers by capillary gas chromatography. 710 58

A scanning electron-microscopic study of experimentally-induced arteriovenous fistulae in rabbits was conducted to investigate the haemodynamically-induced endothelial changes caused by the shunt. Animals were examined from 5 to 696 days postoperatively. The initial endothelial denudation in the vicinity of the anastomosis was rapidly repaired and by 15-20 days re-endotheliazation was complete. Severe surface changes were found in the region of greatest turbulence, opposite the shunt. Changes characteristically consisted of craters, scallops, mounds and ridges, fused together to give a moonscape-like appearance. This area, termed the "jet lesion", was covered with polygonal endothelial cells with thickened, distorted and often highly-crenated margins. The margin of the fistula, where shear stress was expected to be high, exhibited flattened, elongated, generally fusiform endothelial cells with serrated margins. They were aligned parallel to the blood flow, whereas those in the "jet lesion"were polygonal and randomly orientated. These profound changes in the endothelium and the underlying connective tissues, observed as early as 15 days postoperatively, revealed the extent and severity of the effect of haemodynamics on the wall.
Atherosclerosis 1981 Jun
PMID:Scanning electron-microscopic study of the anastomosed vein of arteriovenous fistulae. 725 21

Atherosclerotic plaque with central depression (depressed lesion) was firstly proposed in our previous report as one of the morphological features of regressed lesions, which was characterized by the presence of isolated, well defined lesions with a centrally depressed area and smooth surface. They were obviously different from atherosclerotic plaques with ulceration (ulcerated plaques) in elderly autopsy cases. In this study, 30 ulcerated plaques obtained from specimens of the elderly aortas were histologically and immunohistochemically investigated to clarify the morphogenesis of the depressed lesion and its correlation to the ulcerated plaque. These depressed lesions were divided into 4 groups according to their derivation; (a) fused lesion of multiple fibrous plaques, (b) regressing lesion of plaques, (c) healed ulcerated plaques, and (d) mixed type of these lesions. Regeneration of endothelial cell was noted in the peripheral zone of ulcerated plaques, and collagen type IV was also increased in the stroma of these ulcerated plaques. These were healed ulcerated plaques. The ulcerated plaques with complete restoration of endothelial cells on the ulcerated surface may become atherosclerotic plaques with central depression. These lesions are one of the histological features of regression in advanced atherosclerosis.
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PMID:[Study of atherosclerosis regression in the elderly--central depression and its correlation to ulcerated plaques]. 750 May 54

Hyperlipidemia arises from a disturbance in the balance between production and degradation of lipoprotein particles. Variation in the secretion of human apolipoprotein B (apoB), the major protein component of triglyceride-rich lipoproteins, directly affects this homeostasis. Naturally occurring apoB signal peptide variants (associated with hypertriglyceridemia, altered postprandial lipid metabolism, or atherosclerosis) were investigated for their ability to direct transit through the secretion pathway. Three apoB signal peptide isoforms were fused to the secretory protein, invertase, and expressed in yeast. A deletion or insertion in the hydrophobic core of the signal peptide mediated inefficient translocation into the endoplasmic reticulum and was secretion-defective, relative to the common 27-residue isoform. Additionally, the insertion apoB isoform was observed in yeast to confer a defect in export from the endoplasmic reticulum. Secretion of the apoB signal peptide-invertase fusions responded positively to an inhibitor of calpain type I proteases. These observations suggest that the apoB signal peptide plays a role in determining the levels of apoB degradation and secretion and, thus, hyperlipidemia.
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PMID:Human apolipoprotein B signal sequence variants confer a secretion-defective phenotype when expressed in yeast. 806 10

Contact between low density lipoproteins (LDL) and exocytosed mast cell granules, the "granule remnants," leads to binding of LDL to the granule remnants via ionic interactions between the apolipoprotein B-100 (apoB-100) component of LDL and the heparin proteoglycan component of the granule remnants. Upon incubation at 37 degrees C, the heparin proteoglycan-bound apoB-100 is progressively proteolyzed by remnant chymase and carboxypeptidase A, which are also bound to the heparin proteoglycans. Thereupon, the LDL particles fuse, and their binding to the granule remnants strengthens, as defined by the decreased ability of NaCl to release LDL from the remnants. We now have examined separately the effects of proteolysis and fusion on LDL binding. Proteolysis without fusion was induced by lowering the incubation temperature to 15 degrees C, and proteolysis-independent fusion was induced by treating granule remnant-bound LDL with sphingomyelinase in the presence of protease inhibitors. It was found that degradation of the heparin proteoglycan-bound apoB-100, even without accompanying particle fusion, increased the strength of LDL binding to the granule remnants, suggesting exposure of buried heparin binding regions of apoB-100. When such proteolyzed LDL particles were allowed to fuse, the strength of their binding to the granule remnants increased still further, probably because of an increase in the number of apoB-100 fragments in the enlarged particles. Proteolysis-independent fusion, induced by sphingomyelinase treatment of granule remnant-bound LDL, also increased the strength of binding. The results show that proteolytic degradation and fusion, the two modifications of granule remnant-bound LDL subsequent to action by chymase and carboxypeptidase A of the granule remnants, represent two separate mechanisms by which LDL particles become tightly bound to the heparin proteoglycans of exocytosed mast cell granules. Since the formation of an atheroma, the hallmark of atherosclerosis, is characterized by accumulation in the proteoglycan matrix of the arterial intima of extracellular lipid droplets resembling the fused LDL particles on the granule remnant surfaces, the modifications of LDL described in this study may provide a clue to the actual processes by which the lipid droplets are anchored to the arterial intima.
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PMID:Proteolysis and fusion of low density lipoprotein particles independently strengthen their binding to exocytosed mast cell granules. 829 53

Nonenzymatic glycation of apolipoprotein B (apo B) is a post-secretory modification of low density lipoprotein (LDL) that affects its atherogenic potential and is implicated in the accelerated atherosclerosis associated with diabetes. To facilitate assessment of apo B glycation, we produced hybridomas secreting monoclonal antibodies specific for glycated apo B. SP 2/0 myeloma cells were fused with spleen cells from BALB/c mice immunized with purified apo B glycated non-reductively in vitro. Specificity of monoclonal antibodies secreted by the cloned cell line designated ES12 was demonstrated by immunoblotting and by direct ELISA, wherein the antibodies reacted with glycated epitopes residing in LDL but not in other plasma proteins, and did not react with nonglycated apo B or nonglycated LDL. Immunoblotting of human plasma with ES12 monoclonal antibody yielded an approx. 180,000 molecular weight component showing co-identity with apo B, indicating site specificity for glycated epitopes residing in apo B of the LDL complex and absence of reactivity with other nonenzymatically glycated plasma proteins. This reactivity of ES12 with the physiologic form of glycated apo B that occurs in vivo differs from properties of other antibodies raised against glycated lipoproteins, which recognized glycated residues only after reductive conversion to glucitol-lysine and which do not discriminate between different glycated proteins. In a competitive ELISA, mean concentration of glycated LDL, measured as apo B equivalents, in eight separate plasma samples was 19.7 +/- 1.9 micrograms/ml, representing 3.5 +/- 0.3% of total apo B. The ES12 monoclonal antibody allows specific determination of plasma glycated LDL concentrations, which may have diagnostic and pathogenetic importance.
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PMID:Immunologic detection and measurement of glycated apolipoprotein B with site specific monoclonal antibodies. 850 55


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