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)

The present study reports on the interaction between basal triglyceride and high density lipoprotein (HDL) cholesterol in determining the magnitude of postprandial triglyceridemia. The vitamin A fat-loading test was used to label intestinally derived triglyceride-rich particles after a high fat meal in 18 subjects with low HDL cholesterol and 6 control subjects who had normal fasting triglyceride and HDL cholesterol levels. The patients with low HDL cholesterol were divided into 2 groups on the basis of their basal triglyceride concentrations; 11 had normal triglyceride levels, and 7 had elevated serum triglycerides (HTG). In the HTG-low HDL group, the incremental area under the triglyceride curve was significantly greater (P less than 0.0003) than that in the other 2 groups, between whom no significant differences in triglyceride response were observed. Retinyl palmitate levels measured in whole plasma, an Sf greater than 1000 chylomicron fraction, and an Sf less than 1000 nonchylomicron fraction were also significantly greater in low HDL subjects with HTG, while the concentrations in low HDL subjects with normal triglyceride levels and control subjects were similar. Although basal HDL cholesterol levels in all study subjects were negatively correlated with the area under the incremental triglyceride curve (r = -0.42; P less than 0.05), this correlation was weak, in contrast to the correlation between fasting triglyceride levels and incremental triglyceride area (r = 0.56; P less than 0.005). Furthermore, basal HDL cholesterol levels did not correlate with the area under the chylomicron or nonchylomicron curves, whereas basal triglyceride levels were significantly correlated (P = 0.0001) with both of these variables. The HDL particles of both low HDL groups had a significantly higher proportion of triglyceride compared to the HDL particles in the control subjects. In conclusion, 1) fasting triglyceride levels are a more powerful indicator of the postprandial lipid response than basal HDL cholesterol in subjects with low HDL cholesterol levels; 2) patients with low HDL cholesterol levels do not preferentially accumulate chylomicron remnants after a meal unless they have coexisting hypertriglyceridemia; and 3) abnormalities in the levels of triglyceride-rich particles post-prandially are unlikely to be responsible for the increased incidence of atherosclerosis in low HDL patients who are normotriglyceridemic.
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PMID:Role of basal triglyceride and high density lipoprotein in determination of postprandial lipid and lipoprotein responses. 163 47

The effect of gemfibrozil on postprandial lipoprotein metabolism was investigated in a 12-week, randomized, double-blind, placebo-controlled trial in 20 non-insulin-dependent diabetic patients with moderate hypertriglyceridemia. The patients were given a meal containing 78 g of fat and 345,000 units of vitamin A to label chylomicrons and their remnants. Plasma obtained at various times during the fat-load test was separated into six fractions by gradient-density ultracentrifugation. Gemfibrozil reduced the postprandial triglyceride response, measured as the area under the time-dependent concentration curve, on average by 32% in whole plasma, by 38% in the Svedberg flotation unit (Sf) 1,100-3,200 chylomicron fraction, by 36% in Sf 400-1,100 chylomicrons, and by 38% in the Sf 60-400 lipoproteins. Retinyl palmitate, a measure of intestinally derived particles, was reduced in plasma by 34%, in Sf 1,100-3,200 by 46%, in Sf 400-1,100 by 44%, and in Sf 60-400 by 37%. All these reductions were significant in comparison with the placebo group. Particles with Sf < 60 were not significantly affected. In contrast to earlier observations in healthy subjects, no significant negative correlations existed between postprandial lipemia and high density lipoprotein cholesterol or the postheparin lipoprotein lipase activity. The reduction of the potentially atherogenic chylomicron remnants may decrease the risk of atherosclerosis in non-insulin-dependent diabetes mellitus, a hypothesis that awaits testing in prospective studies.
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PMID:Gemfibrozil reduces postprandial lipemia in non-insulin-dependent diabetes mellitus. 842 63

Hepatic lipase (HL) is an important enzyme in the metabolism of triglyceride-rich lipoproteins and high density lipoproteins. The clinical syndrome of HL deficiency is rare and difficult to identify. We studied carriers of mutant HL to ascertain whether there are distinctive clinical and/or biochemical characteristics of the heterozygous state. In an Ontario kindred, compound heterozygosity for two HL mutations, S267F and T383M, underlies the clinical syndrome of complete HL deficiency. We report that simple heterozygotes for either HL mutant do not have a discrete lipoprotein abnormality, except for relative triglyceride enrichment of lipoprotein fractions with d > 1.006 g/mL. Postheparin HL activity is depressed to a greater degree in carriers of S267F compared with carriers of T383M. Retinyl palmitate loading studies in a compound heterozygote revealed impaired clearance of chylomicron remnants. The dyslipoproteinemia in a compound heterozygote was ameliorated by lovastatin. There was no difference in the quantity and distribution of HL mRNA in the liver of a compound heterozygote when compared with that of a normal subject. Thus, HL deficiency associated with structural variation of the HL gene is characterized by premature atherosclerosis, triglyceride enrichment of lipoprotein fractions with d > 1.006 g/mL, the presence of circulating beta-very low density lipoproteins, and abnormal catabolism of postprandial triglyceride-rich lipoproteins.
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PMID:Hepatic lipase deficiency. Clinical, biochemical, and molecular genetic characteristics. 848 24