Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apolipoproteins are important in the structure and metabolism of lipoproteins, and alterations in levels of apoproteins or in their interrelations occur in some forms of hyperlipemia. Pregnancy is regularly accompanied by hyperlipoproteinemia, but while data on lipoprotein lipids is available, the apopipoproteins have not been studied. To characterize the lipemia of pregnancy more completely, we studied some of the apolipoproteins in plasmas of pregnancy women. Thirty-eight normal fasting women were studied between the 18th and 39th weeks of gestation and again 23 plus or minus 17 weeks after delivery. Eight additional women were sampled every 4-6 wk during the second and third trimesters of gestation. Plasma and lipoprotein lipids were assayed by standard procedures and Apolipoprotein B (ApoB) was measured by radioimmunoassay. The interrelations of Apolipoprotein A (ApoA) in high-density lipoprotein (HDL) and of Apolipoprotein C (ApoC) in very-low-density lipoprotein (VLDL) were assessed by disc gel electrophoresis in four women during the last trimester of gestation and again 6-8 mo post partum and in four nongravid controls. Gestational triglycerides (TG) and cholesterol (Chol) were elevated in 95% of the pregnant women. TG in lipoproteins rose progressively during gestation, with VLDL-TG rising the most. Low-density lipoprotein (LDL) and HDL became enriched by TG relative to other components. Total-and VLDL-ApoB increased, while LDL-ApoB remained unchanged, resulting in a change in the density distribution of ApoB. (VLDL-ApoB X 100/total ApoB rose from 3.6% to 6.7%, P less than 0.02.) The accumulation of TG-rich LDL and the increases of VLDL-ApoB may be the result of changes in the rates of secretion or intravascular catabolism of VLDL. Which process is altered remains to be determined. The relative amounts of ApoC-II and ApoC-III in VLDL and the ApoA-I/ApoA-II ratios in HDL were unchanged in pregnancy. These results differ from those seen following high-carbohydrate diets.
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PMID:Apolipoproteins in human pregnancy. 16 66

Some of the component moieties of high density lipoproteins (HDL) were analyzed in normal subjects and in patients with hyperlipidemia. Apoproteins A-I and A-II were quantified by radioimmunoassay, HDL cholesterol and triglycerides were assessed on heparin-MnCl2 supernates of fasting plasmas. We found that HDL is enriched in triglycerides in all forms of hyperlipidemia, while the proportion of ApoA-II is unaltered and the proportion of ApoA-I is decreased. Thus, the composition of HDL is altered in hupertirglyceridemia. The molecular associations of ApoA-I and ApoA-II in plasma were also examined by assaying the apoprotein contents of plasma fractions prepared by ultracentrifugation and by gel filtration column chromatograpy. The ApoA-I contents of d smaller than 1.063 fraction increased in hyperlipidemia from smaller than 0.5% to approximately 2%, but the ApoA-I contents of the d greater than 1.21 fraction remained at less than 12% of total plasmas with triglyceride levels smaller than 1500 mg/dl. d greater than 1.21 ApoA-I rose to 23% in one plasma with a triglyceride level of greater than 1700 mg/dl. On column chromatography, ApoA-I eluted with the lipoproteins and also in a fraction whose molecular weight (MW) appeared to be approximately 50,000 daltons. The proportion of plasma ApoA-I which eluted in the 50,000 MW peak was positively correlated with plasma triglyceride levels, but at triglyceride levels of less than 1500 mg/dl, less than 20% of ApoA-I was in the 50,000 MW peak. Between levels of approximately 2000 and 12,000 mg/dl, the percentage "50,000 M.W. ApoA-1" was 20-25%. The ApoA-II contents of d smaller than 1.063 fractions were also increased in hyperlipidemia, but greater than 95% of ApoA-II was found in the HDL fractions in both normal and hyperlipidemic plasma both by column chromatography and ultracentrifugation. Thus, the molecular association of ApoA-I appears to be altered in hyperlipidemia.
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PMID:Plasma, apolipoprotein, A-I and A-II levels in hyperlipidemia. 22 Apr 91

The effects of gemfibrozil and lovastatin treatment on composition and hydrated density distribution of high-density lipoprotein (HDL) were studied in 21 patients with heterozygous familial hypercholesterolemia with the use of HDL density gradient ultracentrifugation. At baseline the patients with familial hypercholesterolemia had a markedly reduced or missing HDL2 subfraction and their HDL3 was more dense with reduced content of cholesteryl ester and increased content of triglyceride compared with HDL of control subjects with normal lipid values. Gemfibrozil and lovastatin caused primarily similar alterations in HDL components in HDL2 and HDL3 subfractions. Both agents increased apolipoprotein AI and apolipoprotein AII concentrations significantly in HDL2, whereas the apolipoprotein changes in HDL3 were relatively smaller. The difference between the effects of these two agents was related to the HDL lipid composition. Gemfibrozil increased the cholesterol concentrations of HDL2 and HDL3 (p less than 0.05 for both), and lovastatin caused significant increases in HDL2 (p less than 0.05) and HDL3 phospholipids (p less than 0.01). The observed similarity of qualitative alterations in HDL subfractions produced by these two agents in patients with familial hypercholesterolemia differs from those reported in other types of hyperlipidemia and is probably a consequence of the basic abnormalities in HDL that are characteristic of familial hypercholesterolemia.
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PMID:Effects of lovastatin and gemfibrozil on high-density lipoprotein subfraction density and composition in patients with familial hypercholesterolemia. 161 16

Apolipoprotein (apo) A-II has been biochemically and genetically linked to familial combined hyperlipidemia. Human ApoA-II transgenic mice and peroxisome proliferator-activated receptor alpha (PPARalpha)-deficient mice share some similar phenotypic characteristics. The aim of this study was to determine whether a fibrate-induced PPARalpha activation corrects the combined hyperlipidemia present in human apoA-II transgenic mice. ApoA-II transgenic mice were treated with fenofibrate (250 mg/kg) for 13 days. After this period, they presented a remarkable 8-fold increase in plasma triglycerides. This was concomitant with a 4-fold increase in non-high-density lipoprotein (non-HDL) cholesterol, a quantitatively similar decrease in HDL cholesterol and a severe reduction in mouse plasma apoA-I and apoA-II. Fenofibrate stimulated liver fatty acid beta-oxidation, increased the transcriptional expression of carnitine palmitoyltransferase 1 and phospholipid transfer protein, and decreased expression of apoA-I and apoC-III. However, very-low-density lipoprotein (VLDL)-triglyceride production and lipoprotein lipase (LPL) activities and the expression of other PPARalpha target genes were similar in mice treated with vehicle and fenofibrate. Further, fenofibrate-treated mice presented decreased in vivo [3H]VLDL catabolism and decreased VLDL-triglyceride hydrolysis by exogenous LPL. Therefore, the paradoxical enhancement of hyperlipidemia in fenofibrate-treated apoA-II transgenic mice is mainly due to decreased VLDL catabolism and, also, to a partial impairment in PPARalpha-signaling.
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PMID:Paradoxical exacerbation of combined hyperlipidemia in human apolipoprotein A-II transgenic mice treated with fenofibrate. 1622 89

In the present study, the molecular mechanisms by which CM108, a flavone derivative, improves lipid profiles were investigated further. Hyperlipidaemia was induced by oral administration of high cholesterol and fat. After 4 weeks of treatment, the lipid levels in the serum, liver and faeces were measured and the liver genes involved in lipid metabolism were analysed to explore the molecular mechanisms of lowering lipids. CM108 modulated lipid profiles, including elevating the level of high-density lipoprotein cholesterol (HDL-C; 40%) and reducing serum levels of triglyceride (10%), total cholesterol (10%) and low-density lipoprotein cholesterol (26%). Levels of triglyceride and total cholesterol in the liver were reduced by 18% and 24%, respectively. Increased HDL-C level was attributed to the synergic effects of CM108 in increasing levels of ATP-binding cassette transporter (ABC)A1, apolipoprotein AI and apolipoprotein AII in the liver. Intriguingly, CM108 induced genes, including fatty acid transport protein, acyl-CoA synthetase and lipoprotein lipase that are important for more efficient fatty acid beta-oxidation, thereby reducing serum and liver triglyceride levels. In addition, induction of ABCG5, ABCG8 and cholesterol 7alpha-hydroxylase contributed to cholesterol metabolism, leading to decreases in serum and liver cholesterol levels. Thus, the genes involved in lipid metabolism were systemically modulated by CM108, which contributed to the improvement of lipid profiles in hyperlipidaemic rats.
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PMID:Hypolipidaemic mechanisms of action of CM108 (a flavone derivative) in hyperlipidaemic rats. 1871 25