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

The in vivo turnover of autologous lipoprotein(a) (Lp(a)) was studied in four heterozygous familial hypercholesterolaemic (FH) subjects and four subjects who were hyperlipidaemic but not FH. Each of the FH subjects exhibited a much lower fractional catabolic rate (FCR) for LDL than each of the non-FH subjects. Lp(a) was purified by sequential density gradient centrifugations and was radio-iodinated. The labelled Lp(a) ran as a single band on electrophoresis in gradient polyacrylamide gels. Less than 5% of the label was in lipid, with about 40% of the remainder on apolipoprotein B (apo B) and 60% on apo(a). Labelled and unlabelled Lp(a) competed equally poorly with LDL for binding to LDL receptors on cultured fibroblasts. The FCR of Lp(a), calculated from the decay of the specific radioactivity of the Lp(a) isolated from the daily blood samples, was the same in FH subjects as in non-FH subjects. There was no consistent relationship between Lp(a) FCR and the plasma Lp(a) concentration or between FCR and the Lp(a) phenotype, at least within this sample of subjects. There was a strong association between Lp(a) concentration and production rate, with values for non-FH and FH subjects falling on the same line. The rate of decline of radioactivity in whole plasma was consistently slower than the fall in specific radioactivity of the isolated Lp(a). This difference was more marked in FH subjects than in non-FH subjects and resulted from the accumulation of radioactivity derived from the injected Lp(a) at a lower density than Lp(a), in the fractions containing LDL. The amount of radioactivity in this fraction increased for the first few days after injection and then fell, the fall being more rapid in non-FH than in FH subjects. These results provide no evidence for the involvement of LDL receptors in the catabolism of Lp(a) itself but suggest that they could be responsible for some of the clearance of the lipid and apo B components after removal of apo(a) in the circulation.
Atherosclerosis 1991 Apr
PMID:Catabolism of lipoprotein(a) in familial hypercholesterolaemic subjects. 183 Feb 6

Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) were determined in mentally handicapped subjects (n = 87). 33 women were on lynestrenol 5-10 mg for therapeutic amenorrhea (TA). 18 of them were randomly allocated to continue on lynestrenol and 15 were switched to intramuscular administration of medroxyprogesterone (DMPA). The switch to DMPA resulted in significant increases in HDL-C (33%), Apo A1 (12%), as well as in the HDL-C/LDL-C (48%) and Apo A1/Apo B (22%) ratios. The concentrations of HDL-C and Apo A1 were significantly greater in patients receiving DMPA, than in patients continuing with lynestrenol therapy. The amenorrhea incidence, however, did not differ between the two therapy groups. It is concluded that therapy with DMPA may be associated with smaller atherosclerosis risk than with peroral lynestrenol, because of its weaker effect on HDL-C and A1 levels.
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PMID:Serum lipids and lipoproteins during therapeutic amenorrhea induced by lynestrenol and depot-medroxyprogesterone acetate. 183 88

The authors classify hypertriacylglycerolemias according to their relationship with atherosclerosis as disorders with and without chylomicronemia, atherogenous disorders with an increased level of apolipoprotein B in the VLDL fraction, and relatively harmless (benign) cases. They single out the remarkable heterogeneity of hypertriacylglycerolemias and their epidemiological aspects. The analysis of the various disorders comes complete with their pathobiochemistry and the clinic-biochemical criteria of their classification. The paper also draws attention to a number of possible clinical complications accompanying hypertriacylglycerolemias and their frequency among the population.
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PMID:Hyperlipidemia, dyslipoproteinemia and apolipoproteinopathia--classification and risk of atherosclerosis. Part 3: Hypertriacylglycerolemia. 184 66

Certain proteins (called apolipoproteins B and E) on the surface of lipoprotein particles are responsible for mediating the binding of cholesterol-rich particles to specific lipoprotein receptors on the surface of cells and represent a major pathway controlling blood cholesterol levels. Three important disorders of lipoprotein metabolism, which provide insights into the molecular mechanisms responsible for the elevation of specific atherogenic lipoproteins, are the following: (1) Type III hyperlipoproteinemia results from specific mutations in apolipoprotein E that prevent the normal binding of chylomicron remnants and very-low-density lipoprotein remnants to lipoprotein receptors. Patients with this disorder who have elevated levels of these remnant lipoproteins develop atherosclerosis. (2) Familial defective apolipoprotein B-100 results from a single amino acid substitution in apolipoprotein B that prevents low-density lipoprotein from binding normally to the low-density lipoprotein receptor and elevates plasma cholesterol levels. (3) Familial hypercholesterolemia, which results in elevated levels of plasma low-density lipoprotein and premature atherosclerosis, is caused by a variety of mutations in the low-density lipoprotein receptor that interfere with the normal binding of lipoproteins to this receptor. These observations not only provide insights into the mechanisms responsible for normal lipoprotein metabolism, but also highlight the potential role of specific lipoproteins in atherogenesis.
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PMID:Genetic defects in lipoprotein metabolism. Elevation of atherogenic lipoproteins caused by impaired catabolism. 184 76

Inbred mouse strains C57BL/6J (B6) (susceptible) and C3H/HeJ (C3H) (resistant) differ in atherosclerosis susceptibility due to a single gene, Ath-1. Plasma lipoproteins from female mice fed chow or an atherogenic diet displayed strain differences in lipoprotein particle sizes and apolipoprotein (apo) composition. High density lipoprotein (HDL) particle sizes were 9.5 +/- 0.1 nm for B6 and 10.2 +/- 0.1 nm for C3H. No major HDL particle size subclasses were observed. Plasma HDL level in the B6 strain was reduced by the atherogenic diet consumption while the HDL level in the resistant C3H mice was unaffected. The reduction in HDL in the B6 strain was associated with decreases in HDL apolipoproteins A-I(-34%) and A-II(-60%). The HDL apoC content in mice fed chow was two-fold higher in C3H than B6. Lipoproteins containing apolipoprotein B (VLDL, IDL, LDL) shifted from a preponderance of the B-100 (chow diet) to a preponderance of the B-48 (atherogenic diet). The LDL-particle size distribution was strain-specific with the chow diet but not genetically associated with the Ath-1 gene. In both strains on each diet, apolipoprotein E was largely distributed in the VLDL, LDL, and HDL fractions. The B6 strain became sixfold elevated in total lipoprotein E content which in the C3H strain was not significantly affected by diet. However, the C3H LDL apoE content was reduced. On both diets, the C3H strain exhibited apolipoprotein E levels comparable to the atherogenic diet-induced levels of the B6 mice.
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PMID:Effects of atherogenic diet consumption on lipoproteins in mouse strains C57BL/6 and C3H. 185 5

The major components of atherosclerotic plaque, ultimately responsible for clinical effects, are deposited lipids--mostly cholesteryl esters and cholesterol, derived largely from the lower-density lipoproteins of the blood--and proliferated, modified arterial smooth muscle cells with their synthesized connective tissue products. Advanced plaques vary widely in the proportion of the two components, but evidence indicates that lipid deposition--especially of lipoprotein elements--often occurs in the lesion-prone intimal areas of the artery prior to the buildup of smooth muscle cells. The 1980s were remarkably productive for investigators who study the pathogenesis of atherosclerosis. We now know of the many forms of lower-density lipoproteins, i.e., low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), some of which are more likely to be associated with accelerated atherosclerosis and some of which are more likely to be influenced by diet. Among these forms of LDL and VLDL are LDL-1, beta-VLDL, and Lp(a). Work has been reported implicating various alterations of endothelial function in the permeability of the arterial endothelial barrier in the transport of these low-density, cholesterol-rich macromolecules. Of possibly greater interest is the developing evidence that such proliferation-stimulating molecules as platelet-derived growth factor (PDGF) can be produced by a number of cells likely to be involved in the progression of atherosclerotic plaque. In addition to platelets, these include activated monocytes and monocyte-derived macrophages, injured endothelial cells, and smooth muscle cells, which can undergo an autocrine conversion to PDGF synthesis--possibly stimulated by LDL from hyperlipidemic serum. Leukotrienes and other endothelium-associated regulatory molecules may also take part in the paracrine and autocrine mechanisms of stimulating smooth-muscle-cell proliferation. Additional recent developments that have led to a better understanding of atherosclerotic pathogenesis have occurred. The first is evidence of the involvement of oxidized LDL and its apolipoprotein B in atherogenesis. Research indicates that antioxidants have a suppressive effect on atherogenesis when oxidized LDL has been involved in lesion development. The data linking the development of autoimmune reactions to these oxidatively altered lipoproteins are also impressive. Further, there is increasing evidence that atherogenesis in nonhuman primates and in people in whom chronic sustained circulating immune complexes are involved is likely to be accelerated, even when few or no classic risk factors are present. These lesions appear to represent a distinct microarchitectural form of concentric and transmural atherosclerosis that is better classified as "atheroarteritis."
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PMID:Update on the pathogenesis of atherosclerosis. 186 33

The effect of drinking pattern on plasma lipoproteins and body weight was examined in three groups of squirrel monkeys: (1) controls fed isocaloric liquid diet; (2) regular drinkers given liquid diet containing ethanol (EtOH) substituted isocalorically for carbohydrate at 12% of calories daily; and (3) binge drinkers fed 6% EtOH calories daily for a four-day period followed by three days of 20% EtOH to mimic a weekend bout drinking cycle. The number of calories offered per day was the same for all groups, and the average weekly EtOH consumption (12% calories) was identical for the two alcohol treatments. The entire study lasted six months. There were no significant differences in plasma cholesterol, triglyceride or liver function tests. Regular drinkers had the highest high density lipoprotein2/high density lipoprotein3 (HDL2/HDL3) protein and apolipoprotein A-I/B ratios of any group and exhibited a significant elevation in the molar plasma lecithin:cholesterol acyltransferase (LCAT) rate (nmol/min/ml). Binge drinking produced a selective increase in low density lipoprotein (LDL) cholesterol and apolipoprotein B, and a depression in the fractional LCAT rate (% esterified/min). During the course of the study, controls ate 92% of their diet while the alcohol groups each consumed 95% of the liquid diet. Despite this difference, body weight and Quetelet index (weight/height2) decreased progressively in the order controls greater than regular drinkers greater than binge drinkers. Results from our study indicate that moderate, regular daily consumption of EtOH at 12% of calories causes a modest reduction in body weight and produces a coronary protective lipoprotein profile (increases HDL2/HDL3, increases apolipoprotein A-I/B, low LDL cholesterol). By contrast, when this same average weekly dose is concentrated in a binge cycle, unfavorable alterations in lipoprotein composition (increases LDL cholesterol, increases apolipoprotein B) and metabolism (decreases LCAT activity) occur along with weight loss and depletion of body fat. These studies point to the value of the squirrel monkey model in evaluating both favorable and pathophysiological effects of chronic EtOH intake.
Atherosclerosis 1991 May
PMID:Effect of drinking pattern on plasma lipoproteins and body weight. 187 9

We studied the levels of cardiovascular risk factors in a population sample of 511 men and 920 women aged 65-74 years and living in East Finland. Altogether 312 men and 515 women had normal glucose tolerance, 84 men and 158 women impaired glucose tolerance (IGT), 33 men and 59 women newly diagnosed non-insulin-dependent diabetes (NIDDM) detected at the survey, and 82 men and 188 women previously diagnosed NIDDM. Subjects with IGT or newly diagnosed NIDDM had higher levels of total triglycerides and apolipoprotein B and lower levels of HDL cholesterol and apolipoprotein A1 than subjects with normal glucose tolerance, similarly as in previously diagnosed NIDDM. Furthermore, subjects with IGT or newly diagnosed NIDDM were more obese, had higher waist-hip ratio, and more frequently hypertension than subjects with normal glucose tolerance. Thus, asymptomatic hyperglycemia in the elderly is not a benign phenomenon, but is associated with similar adverse changes in cardiovascular risk factors as in middle-aged subjects.
Atherosclerosis 1991 Jun
PMID:Asymptomatic hyperglycemia and cardiovascular risk factors in the elderly. 189 82

The plasma concentrations and chemical compositions of the apolipoprotein B containing lipoproteins (VLDL, IDL and LDL) were studied in 29 male alcoholic subjects at the end of a drinking period and in 17 healthy controls. No difference was found in the concentrations of plasma total cholesterol and triglyceride between the alcoholics and the controls, whereas plasma HDL cholesterol and VLDL triglycerides were 90% and 73%, respectively, higher in the alcoholics. The VLDL cholesterol:triglyceride ratio was reduced by 32%, whereas VLDL protein:cholesterol and phospholipid:cholesterol ratios were increased by 36% and 46%, respectively. IDL mass and protein concentrations, and particularly the fractional cholesteryl ester content of IDL tended to be low in the alcoholics. The plasma concentrations of all the LDL components except triglycerides were reduced in the alcoholics, resulting in a lower LDL cholesterol:triglyceride ratio. During the four day abstinence, when the lipoprotein values were followed in 15 alcoholic subjects, the abnormalities in VLDL composition and LDL plasma concentrations changed towards the values of the controls. In six alcoholic subjects who volunteered for LDL kinetic studies the fractional catabolic rate for LDL particles isolated immediately after the drinking period and seven days later were the same. These studies suggest that the alterations in all the apoB containing lipoproteins may contribute to the delayed progression of atherosclerosis observed in alcohol users.
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PMID:Multiple changes in apoprotein B containing lipoproteins after ethanol withdrawal in alcoholic men. 193 Sep 37

Reduction of the blood levels of low density lipoprotein (LDL) is important for lowering the incidence of atherosclerosis. In this study, LDL was directed to rat parenchymal liver cells by lactosaminated Fab fragments of anti-apolipoprotein B antibodies (LacFab). We followed the fate of intravenously injected complexes of LacFab and [3H]cholesteryl oleate-labeled LDL. Complexing of LacFab to LDL led to rapid disappearance of LDL from the circulation. At 30 minutes after injection, the liver contained 58.5 +/- 9.0% of the injected dose (at that time the liver contained only 5.7 +/- 2.2% of an injected dose of free LDL). Liver uptake was blocked by N-acetylgalactosamine but not by N-acetylglucosamine, which indicates that galactose-specific recognition sites are responsible for the LacFab-induced hepatic uptake. By isolating liver cells, it was found that parenchymal, endothelial, and Kupffer cells account for 87%, 3%, and 10% of the total hepatic uptake, respectively. Subcellular fractionation of the liver indicated that the complexes are rapidly internalized and transported to lysosomes. Within 1 hour after injection, virtually all the [3H]cholesteryl oleate of the internalized LDL was hydrolyzed; hydrolysis was followed by excretion of radioactivity into the bile. Compared with rats injected with native [3H]cholesteryl oleate-labeled LDL, eight times as much radioactivity was excreted into the bile during the first 4 hours after the injection of LacFab-complexed [3H]cholesteryl oleate-labeled LDL. Thus, LacFab induces enhanced hepatic uptake of LDL via galactose receptors on the parenchymal cells, followed by processing in lysosomes and excretion into the bile. In this way, LacFab induces an increased irreversible removal of LDL cholesterol from the body.
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PMID:Enhanced hepatic uptake and processing of cholesterol esters from low density lipoprotein by specific lactosaminated Fab fragments. 193 82


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