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

The JCR:LA-corpulent rat is an obese, hyperlipidemic, hyperinsulinemic strain that is atherosclerosis-prone and develops myocardial lesions. The hyperlipidemia is due to elevated plasma levels of a large relatively triglyceride-rich very low density lipoprotein (VLDL). Both corpulent and lean male and female rats were studied. Postheparin lipid clearance and apparent hepatic secretion rate after Triton WR1339 inhibition of lipoprotein lipase were determined. The concentrations of cholesterol and cholesteryl esters were not significantly altered by either treatment. Triglycerides showed rapid postheparin clearance in corpulent rats. The apparent hepatic secretion rate was markedly higher in corpulent male rats than in lean male rats, and the rate in corpulent females was again higher, reflecting the higher serum triglyceride concentrations in corpulent female rats. The relative secretion rate of C:48 triglyceride molecular species was lower than that of the C:50 to C:56 species, while the postheparin clearance of C:48 triglyceride molecular species was impaired compared to the C:50 species and those with higher carbon numbers. This effect was more marked in the male than in the female corpulent rats. The results indicate that VLDL hyperlipidemia in the corpulent rat is due to hepatic hypersecretion of VLDL and not to a defect in lipoprotein lipase. Further, the atherogenesis that is characteristic of the corpulent male rat may be related to the differential metabolism of fatty acids.
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PMID:Plasma lipid secretion and clearance in hyperlipidemic JCR:LA-corpulent rats. 259 65

Hypertriglyceridemic (HTG) serum, lipolyzed in vitro by purified bovine milk lipoprotein lipase, was found to be cytotoxic to cultured macrophages. Surviving macrophages contained numerous lipid inclusions similar to those found in foam cells. Individual lipoprotein fractions isolated from the lipolyzed HTG serum, including HDL, were also cytotoxic. Lipolysis of isolated lipoprotein fractions (either HTG or normal) allowed localization of cytotoxicity to postlipolysis remnant VLDL and chylomicron particles. The presence of a critical concentration of HDL in either the lipolysis mixture or the culture dishes inhibited the cytotoxicity. Below this critical concentration HDL itself became cytotoxic, producing lipid inclusions in surviving macrophages. The lipid fraction of the cytotoxic remnants contained the cytotoxic factor(s); neither FFA nor lysolecithin alone could account for this cytotoxicity. Postprandial lipemic sera from subjects with a brisk chylomicron response, when lipolyzed in vitro, were cytotoxic to cultured macrophages; neither fasted sera from these subjects, nor postprandial sera from normolipidemic subjects with a normal chylomicron response, were cytotoxic. Postheparin (in vivo lipolyzed) serum and its isolated lipoprotein fractions obtained 30 min after heparin injection in subjects with HTG were shown to be cytotoxic to macrophages; by 60 min most of the cytotoxicity had disappeared. The postprandial and postheparin observations support an in vivo significance for remnant-associated cytotoxicity. We hypothesize that cytotoxic remnants of lipolyzed VLDL and chylomicrons may be one of the major atherogenic lipoproteins. Further, we suggest that inhibition of the cytotoxicity of these remnants may be one important way that HDL prevents atherosclerosis.
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PMID:Lipolytic surface remnants of triglyceride-rich lipoproteins are cytotoxic to macrophages but not in the presence of high density lipoprotein. A possible mechanism of atherogenesis? 270 36

Cessation of smoking is followed by a rapid rise in plasma HDL concentrations. An earlier study has demonstrated a significant relationship between the increase in HDL concentrations and spontaneous changes in food intake, specifically an increased fat intake. In this investigation we have dissociated the effects of cessation of smoking as such from those of dietary alterations by monitoring plasma lipid and lipoprotein concentrations after cessation of smoking in 12 subjects whose diet was kept constant during an initial 2-week control period and during 2 weeks following cessation of smoking. Under these conditions plasma HDL-cholesterol levels did not increase significantly (1.01 +/- 0.26 mmol/l (mean +/- SD) before and 1.04 +/- 0.27 mmol/l after cessation of smoking). Similarly, no significant alterations were recorded for other plasma lipid or lipoprotein concentrations. Activities of lipoprotein lipase and hepatic lipase were unchanged throughout the study. These results suggest that the marked rise in HDL concentrations after stopping smoking is largely related to spontaneous changes in dietary habits which occur upon cessation of smoking.
Atherosclerosis 1989 Feb
PMID:High density lipoprotein concentrations after cessation of smoking: the importance of alterations in diet. 271 63

The etiology of the hypertriglyceridemia in alloxan-diabetic rabbits was studied by two independent methods. Production and removal rates of VLDL triacylglycerol were measured in diabetic rabbits by injection of [3H]palmitate-labelled VLDL. Similarly, triacylglycerol total removal rates were determined in non-diabetic rabbits which were infused with Intralipid to mimic the plasma triacylglycerol concentrations of diabetic rabbits. Compared to nondiabetic rabbits, triacylglycerol removal rats were decreased in diabetic rabbits, particularly at higher levels of plasma triacylglycerol. During cholesterol and triacylglycerol supplementation of the diet, post-heparin plasma lipoprotein lipase activity of diabetic rabbits with severe hypertriglyceridemia averaged 36% of that of nondiabetics, suggesting an impaired triacylglycerol removal capacity. Furthermore, plasma triacylglycerol was inversely related to post-heparin plasma lipoprotein lipase activity among diabetic rabbits. VLDL triacylglycerol production increased with increasing plasma triacylglycerol concentration among diabetic cholesterol-fed rabbits with moderately severe hypertriglyceridemia, but reached an apparent plateau among rabbits with plasma triacylglycerol concentrations from approx. 2000-9000 mg/dl. Thus, severe hypertriglyceridemia in this model of insulin deficiency can be attributed only partially to VLDL hypersecretion, whereas a removal defect, resulting in saturation of the triacylglycerol removal mechanism, appears to be largely responsible. The impaired removal of plasma triacylglycerol is also related to the presence of cholesterol predominantly in lipoproteins of increased size. The data support the hypothesis that protection against atherosclerosis in cholesterol-fed diabetic rabbits results from exclusion of very large cholesterol-containing lipoproteins from the arterial wall.
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PMID:Impaired triacylglycerol catabolism in hypertriglyceridemia of the diabetic, cholesterol-fed rabbit: a possible mechanism for protection from atherosclerosis. 271 83

Levels of plasma lipoproteins and lipoprotein lipase activities in post-heparin serum were measured in 24-h fasted pigs which were fed a diet containing either 21 energy % mackerel oil or 21 energy % lard fat for 8 weeks. Lipoprotein fractionation was performed separately by density gradient ultracentrifugation and agarose gel chromatography. After 8 weeks levels of plasma triacylglycerol (-62%) and cholesterol (-55%) were lower in the mackerel oil than in the lard fat-fed animals. The triacylglycerol decline was exclusively due to the VLDL fraction, while cholesterol was reduced in all lipoprotein fractions (VLDL, IDL, LDL and HDL). Lipoprotein lipase activity in post-heparin serum, taken 6 h after a meal, was 31% decreased in mackerel oil-fed animals. The results support the hypothesis that regular intake of fish oil reduces VLDL secretion.
Atherosclerosis 1989 May
PMID:Effects of diets supplemented with lard fat or mackerel oil on plasma lipoprotein lipid concentrations and lipoprotein lipase activities in domestic swine. 271 57

The aim of this study was to characterize the plasma lipoprotein pattern and some aspects of cholesterol metabolism in a line of hyperlipemic male rats. Plasma cholesterol and triglycerides were increased about 3-fold as compared to control animals (238 vs. 75 and 185 vs. 59 mg/dl respectively). The plasma lipoprotein distribution and the chemical composition of the isolated lipoproteins was unaffected. Plasma triglyceride production rate was increased (40%, P less than 0.01) and post-heparin lipoprotein lipase activity in plasma decreased (-28%, P less than 0.01) in the hyperlipemic rat. The activity of 3 enzymes involved in cholesterol metabolism (HMG-CoA reductase, cholesterol 7 alpha-hydroxylase, and acyl-CoA cholesterol-acyltransferase) did not differ from control values. 3H2O incorporation into digitonin-precipitable sterols, however, was significantly higher than in controls. This finding was due, in part, to an increased liver weight in the hyperlipemic animals. Furthermore kinetic data using 125I-LDL showed that the fractional catabolic rate of lipoprotein was within the normal range, while the synthetic rate of LDL protein was increased (0.67 vs. 0.3 mg/kg/h, P less than 0.01) in the hyperlipemic rat. These observations suggest that multiple metabolic defects underline the hyperlipemia observed in this animal model.
Atherosclerosis 1989 Apr
PMID:Plasma lipoproteins and cholesterol metabolism in spontaneously hyperlipemic rats. 273 Jul 13

Lipoprotein lipase is a rate determining enzyme for the removal of triglyceride-rich lipoproteins from the blood stream. We examined whether genetic variation at the lipoprotein lipase gene locus was related to the fasting plasma level of triglycerides in both a normal and hypertriglyceridaemic population. Two restriction fragment length polymorphisms revealed by the enzymes PvuII and HindIII generated alleles designated H1, 17.5 kb;H2, 8.7 kb;P1, 7.0 kb;P2, 4.4 and 2.5 kb, respectively. These were studied in 46 Caucasian hypertriglyceridaemic subjects in comparison with 86 normolipidaemic controls. The respective allelic frequencies were H1 0.211, H2 0.789 and H1 0.414, H2 0.586 (p less than 0.01). Similar differences in allelic frequencies were found in a smaller group of Japanese hypertriglyceridaemic subjects (n = 29) compared to Japanese controls (n = 41, p less than 0.01). Ninety-three healthy Caucasians were genotyped for both polymorphic sites to relate to levels of plasma triglyceride. We found that individuals with genotype P1P1 had fasting triglyceride levels of 0.96 +/- 0.31 mmol/l (n = 20) compared to genotype P2P2 with levels of 1.31 +/- 0.66 mmol/l (n = 30, p less than 0.02); heterozygous subjects (P1P2) had intermediate levels of plasma triglyceride (1.15 +/- 0.46 mmol/l, n = 43). The HindIII alleles were not significantly associated with variation in levels of plasma triglyceride, cholesterol, or HDL-cholesterol. We conclude that DNA variations at, or around, the lipoprotein lipase gene may constitute genetic determinants for both the population variation in plasma triglyceride levels as well as for the common metabolic disorder of primary hypertriglyceridaemia.
Atherosclerosis 1989 Sep
PMID:DNA polymorphisms at the lipoprotein lipase gene: associations in normal and hypertriglyceridaemic subjects. 280 49

Following the recent demonstration that both cholestyramine and nicotinic acid decrease mortality from coronary heart disease, there is a new enthusiasm for hypolipidaemic therapy. The agents in current use are, however, insufficiently active or are accompanied by unacceptable side effects. An understanding of the mode of action is necessary, both to optimize treatment guidelines (e.g. regarding combination therapy or use in specific subsets of patients) and to develop new agents with preferred actions on rate-limiting steps. A reduction in LDL cholesterol concentration remains the principal desired action, although an elevation in HDL may also be beneficial. The main categories of commercially available agent comprise the anion exchange resins (inhibitors of bile acid absorption); cholesterol absorption inhibitors; fibrates (probably acting by enhancing lipoprotein lipase); and probucol (affecting LDL clearance). The most interesting of the new agents in clinical trials are the beta-hydroxy-beta-methylglutaryl-CoA reductase inhibitors, but other types of agent are at an earlier stage of evaluation, e.g. acyl-CoA: cholesterol acyltransferase inhibitors and peptide cofactors. It is not yet certain whether all the approaches to cholesterol lowering have equal validity, although an effect on biological endpoints is obtained for a variety of agents. Future evaluation will be aided by the implementation of noninvasive methods to quantify atherosclerosis and by the use of simple, 'dry-chemistry', cholesterol assays to screen populations.
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PMID:Mode of action of lipid-lowering drugs. 289 41

In severe cystic acne we found low levels of high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A (Apo-A) in the presence of normal total lipids. In a larger number of patients, we always observed significantly lower levels of HDL-C and Apo-A than in either age-matched controls or subjects with acne vulgaris. Since lipoprotein lipase is one major determinant of HDL concentration, we assayed the lipase activity in liver and extra-hepatic tissues by the method of Krauss et al. There was highly significant less total and hepatic lipase activity than in age-matched controls. HDL distribution was examined by zonal ultracentrifugation and a decrease in the HDL2 subclass was discovered. Since HDL are inversely correlated to atherosclerosis, cystic acne is one risk factor for atherosclerosis. The linkage between low HDL levels and severe cystic acne should be further investigated.
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PMID:Lipoprotein metabolism and lipoprotein lipase in severe cystic acne. 293 79

Rat mesenteric lymph chylomicrons, containing triglycerides enriched with either [14C]oleic acid or [14C]eicosapentaenoic acid, were prepared by ultracentrifugation of lymph samples collected for 6 h after a single duodenal infusion of an emulsion containing 0.3 mmol of either fatty acid. After determination of protein and of total fatty acid content and composition, enriched chylomicrons were suspended in Krebs-bicarbonate buffer. Non-working hearts were perfused in a recirculating system for 45 min using the enriched chylomicron preparations. At 15 min intervals during perfusion, the media were assayed for total radioactivity, 14CO2 and 14C-labeled fatty acids associated with triglycerides, unesterified fatty acids, phospholipids, mono- and diglycerides. After perfusion, the hearts were extracted and assayed for total lipid radioactivity and isotope distribution among heart lipid fractions. With this membrane-supported lipoprotein lipase system, clearances of chylomicron triglycerides containing either fatty acid were identical, as were the myocardial uptakes of the fatty acids and oxidations to 14CO2. Furthermore, except for a significantly greater incorporation of eicosapentaenoate into myocardial phospholipids, tissue isotope distributions of the two labeled fatty acids were also the same. These studies suggest that at least the initial phases of peripheral clearance of chylomicrons enriched in omega-3 fatty acids is as efficient as with those containing oleate.
Atherosclerosis 1987 Jun
PMID:In vitro clearance of chylomicron triglycerides containing (omega-3) eicosapentaenoate. 304 21


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