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)

Labeling of apolipoprotein C-I by the Bolton and Hunter reagent allowed a study of the kinetics of this peptide in normolipidemic human volunteers. After its intravenous injection the appearance of radioactivity of the labeled apoprotein was followed in plasma, lipoprotein fractions, and urine for 15 days. Apolipoprotein C-I was quickly associated with HDL and to a smaller extent with VLDL in in vitro and in vivo incubation. Kinetic parameters of apolipoprotein C-I were compared with those of apo A-I. Fractional catabolic rates are respectively 0.422 +/- 0.044 vs 0.240 +/- 0.003 pools/day, residence times through the whole system 3.24 +/- 0.27 vs 6.31 +/- 0.27 days and production rates 1.79 +/- 0.18 vs 13.2 +/- 2.1 mg/kg X day. Two explanations for these differences are proposed.
Atherosclerosis 1986 Nov
PMID:Metabolism of apolipoprotein C-I in normolipoproteinemic human subjects. 309 3

Apolipoprotein C-I (apoC-I) has been proposed to act primarily via interference with apoE-mediated lipoprotein uptake. To define actions of apoC-I that are independent of apoE, we crossed a moderately overexpressing human apoC-I transgenic, which possesses a minimal phenotype in the WT background, with the apoE-null mouse. Surprisingly, apoE-null/C-I mice showed much more severe hyperlipidemia than apoE-null littermates in both the fasting and non-fasting states, with an almost doubling of cholesterol, primarily in IDL+LDL, and a marked increase in triglycerides; 3-fold in females to 260 +/- 80 mg/dl and 14-fold in males to 1409 +/- 594 mg/dl. HDL lipids were not significantly altered but HDL were apoC-I-enriched and apoA-II-depleted. Production rates of VLDL triglyceride were unchanged as was the clearance of post-lipolysis remnant particles. Plasma post-heparin hepatic lipase and lipoprotein lipase levels were undiminished as was the in vitro hydrolysis of apoC-I transgenic VLDL. However, HDL from apoC-I transgenic mice had a marked inhibitory effect on hepatic lipase activity, as did purified apoC-I. LPL activity was minimally affected. Atherosclerosis assay revealed significantly increased atherosclerosis in apoE-null/C-I mice assessed via the en face assay. Inhibition of hepatic lipase may be an important mechanism of the decrease in lipoprotein clearance mediated by apoC-I.
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PMID:Overexpression of apoC-I in apoE-null mice: severe hypertriglyceridemia due to inhibition of hepatic lipase. 1245 76

An Hpa I restriction site located 317 bp upstream of the transcription initiation site of the apoC-I gene has been shown to increase apoC-I gene transcription in vitro. The aim of the present study was to determine whether this genetic polymorphism was associated in vivo with increased plasma levels of apoC-I. In a cohort of French-Canadians (n=391) recruited for a family study, we found strong linkage disequilibrium between the genes for apoC-I and apoE (as reported before for European-Americans), such that the apoC-I Hpa I-negative (H1) allele was strongly associated with apoE epsilon 3, whereas the apoC-I Hpa I-positive (H2) allele was strongly associated with apoE epsilon 2 and epsilon 4. ApoC-I and apoE were measured by ELISA in total plasma and in very low-density lipoproteins (VLDL) separated by ultracentrifugation (d<1.006 g/ml), and then by difference for the non-VLDL fraction (d>1.006 g/ml), in a subset of families selected for their diverse apoE genotypes. Subjects were divided into normolipidemic (NL, n=89, TG<2.3 mmol/l, LDL-C<3.8 mmol/l) and hyperlipidemic groups (HL, n=88, TG>2.3 mmol/l and/or LDL-C>3.8 mmol/l). In NL subjects, apoC-I levels were not significantly associated with apoC-I genotype (H1/H1, H1/H2 or H2/H2). They were, however, related to apoE genotype, such that apoE3/2 subjects tended to have higher and apoE4/3 subjects tended to have lower concentrations of total plasma and non-VLDL apoC-I and apoE. Total plasma, VLDL and non-VLDL apoC-I and E levels were also higher in HL subjects with an apoE2/2 or apoE3/2 genotype. These results suggest that plasma levels of apoC-I are more strongly influenced by apoE genotype than by the Hpa I apoC-I promoter polymorphism, which probably reflects an effect of different apoE isoforms on plasma lipoprotein and plasma apoC-I metabolism, rather than a direct effect of apoE alleles on apoC-I transcription.
Atherosclerosis 2003 Jul
PMID:Plasma concentration and lipoprotein distribution of ApoC-I is dependent on ApoE genotype rather than the Hpa I ApoC-I promoter polymorphism. 1286 Feb 51

Apolipoprotein (apo) E and C-I are plasma apolipoproteins that have been implicated in the etiology of atherosclerosis and obesity, respectively. Both proteins are synthesized and secreted by macrophages, though pharmacological regulation of their production is poorly understood. The authors compared the effect of 2 HMG-CoA reductase inhibitors, atorvastatin and cerivastatin, on the synthesis and secretion of apoE and apoC-I by THP-1 macrophages. Atorvastatin reduced medium apoE and cellular apoE mRNA of PMA-activated THP-1 cells in a dose-dependent manner (-24% and -22%, respectively, at 1-micromol/L, P < 0.01). ApoC-I in the medium was also reduced by atorvastatin in a dose-dependent manner, though to a lesser extent (-15% at 1-micromol/L, P < 0.05). Cerivastatin similarly reduced medium apoE (-20% at 1-micromol/L, P < 0.05) and cellular apoE mRNA (-31% at 1-micromol/L, P < 0.05), and significantly lowered cellular apoC-I mRNA (-15%, P < 0.05), but not apoC-I in the medium. In experiments with THP-1 macrophages loaded with cholesterol (ie, 24-hour incubation with acetyl-LDL), atorvastatin and cerivastatin (1-micromol/L) significantly (P < 0.05) reduced both medium apoE (-30% and -25%, respectively) and cellular apoE mRNA (-25% and -17%, respectively). A lower and less consistent effect was observed on medium apoC-I (-6% and -18%, respectively) and cellular apoC-I mRNA (-13% and -19%, respectively). These data demonstrate that statins have the capacity to reduce the synthesis and secretion of both apoE and apoC-I in THP-1 macrophages loaded or unloaded with cholesterol.
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PMID:Effect of atorvastatin on ApoE and ApoC-I synthesis and secretion by THP-1 macrophages. 1288 30

ApoC-I plays an important role in controlling plasma lipid metabolism, however little is known about factors regulating the hepatic synthesis and secretion of this apolipoprotein. In the present study, we have carried out experiments with human hepatoma (HepG2) cells, in order to determine the effect of different tissue culture conditions on cellular lipid levels and on the production of apoC-I (and apoE) at the protein and mRNA level. Cells incubated for 48 h with 10% human serum had significantly higher cellular triglyceride (22%, P<0.05) and cholesterol levels (19%, P<0.01), higher medium apoC-I and apoE levels (2.6- and 2.9-fold, respectively), but similar levels of apoC-I and apoE mRNA, compared to cells incubated with 10% human lipoprotein-deficient serum (LPDS). Serum containing only HDL, or containing HDL with LDL, also increased cellular lipids and increased secreted apoC-I and apoE levels without altering apoC-I and apoE mRNA levels. Incubation of cells with Intralipid triglyceride (625 microM), increased cellular triglyceride (2.8-fold, P<0.001), decreased cellular cholesterol (32%, P<0.01), decreased cellular and medium apoC-I (24 and 26%, P<0.01) and had no effect on apoC-I mRNA levels. Additional experiments in which cells were loaded with cholesterol (incubation with 10 microg/ml cholesterol plus 1 microg/ml 25-hydroxycholesterol) or depleted of cholesterol (statin treatment) confirmed that secretion of apoC-I by HepG2 cells was dependent on cellular cholesterol levels and independent of changes in apoC-I mRNA levels. These results demonstrate that cellular cholesterol rather than triglyceride levels play a role in controlling apoC-I production by HepG2 cells and that this regulation occurs at a post-transcriptional level.
Atherosclerosis 2005 Feb
PMID:Post-transcriptional regulation of apoC-I synthesis and secretion in human HepG2 cells. 1569 32

Over the last decade, C-reactive protein concentration analyzed by the high sensitivity method (hsCRP) has been proven as a marker of premature atherosclerosis. Concentration exceeding 2 mg/l represents an increased individual risk of myocardial infarction and stroke but strict application of this borderline is complicated by relations of CRP concentrations to other risk factors of cardiovascular diseases. In a large 1 % representative sample of the Czech population, a positive relation of hsCRP to BMI, a waist circumference and triglyceride concentration was documented. Substantial sex differences were found in its relationship to age. Whereas it is continuously increasing in men, this increase appears in women only after menopause. A substantial decrease of body weight and visceral fat volume by increased physical activity is accompanied by significant decrease of hsCRP in young obese women. This decrease was not related to a change of interleukin-6 concentration, although it is supposed to regulate CRP production. CRP concentration is partly under genetic control as a higher concentration in young siblings of probands with proved coronary atherosclerosis was documented. The participation of genes related to lipoprotein metabolism (genes for apolipoprotein CI and apolipoprotein E) influence hsCRP concentrations. We hypothesized that an increased concentration of hsCRP represents a certain marker of proinflammatory status related to central obesity and triglyceride metabolism and it might be related to individual properties of monocytes in atherogenesis.
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PMID:Proinflammatory status, genetics and atherosclerosis. 2013 29