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)

Apolipoprotein A-1 (Apo A-1) is the major protein constituent of high-density lipoprotein (HDL) and Apo A-1 plays an important role in lipid metabolism and may be protective against atherosclerosis in adults. However, little is known about HDL and Apo A-1 in the developing human fetus. Herein we investigated the relationship of Apo A-1 levels in umbilical cord blood at delivery to gestational age and HDL cholesterol. Fetal plasma levels of Apo A-1, which were not correlated with those in maternal plasma, were significantly lower among newborns delivered at 21-26 wk gestation (52 +/- 4.4 mg/dl, mean +/- SE) than in those delivered at 33-34 wk gestation (87 +/- 5.8 mg/dl). Thereafter, the mean umbilical cord plasma levels of Apo A-1 remained relatively constant (101 mg/dl at 39-40 wk of gestation). We found no significant correlations between Apo A-1 levels and fetal sex, race, or delivery method. At equivalent gestational ages and birth weights, however, Apo A-1 levels in white newborns tended to be lower than those in black infants. The Apo A-1/HDL cholesterol ratio in umbilical cord blood rose progressively from 2.5 (27-28 wk gestation) to 3.8 at term, due largely to increased Apo A-1 levels but little change in the mean HDL cholesterol levels, which ranged from 22-24 mg/dl at each gestational period. These results are suggestive that fetal plasma Apo A-1 is derived solely from fetal sources and that the rate of production and/or clearance of Apo A-1 is altered during the latter third of human intrauterine development.
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PMID:Apolipoprotein A-1 in umbilical cord blood of newborn infants: relation to gestational age and high-density lipoprotein cholesterol. 313 25

Retrospective analysis of ulcer healing trials utilizing enprostil, a synthetic dehydroprostaglandin E2 analogue, has demonstrated a 10% or greater reduction in total serum cholesterol in 64%, 64% and 67%, respectively, of hypercholesterolemic subjects receiving the drug in doses of 70 micrograms, 35 micrograms, and 7 micrograms bid, respectively. Only 16% of subjects receiving placebo exhibited a similar reduction (P less than 0.05). The median percent changes for hypercholesterolemic patients receiving enprostil 70 micrograms, 35 micrograms, or 7 micrograms bid, and placebo were -17%, -13%, -11%, respectively, while the median percent change for those on placebo was 0% (P less than 0.05). Eight normocholesterolemic subjects participated in a double-blind crossover study comparing enprostil 70 micrograms/d with its placebo. Nine days of enprostil administration was associated with reductions in total serum cholesterol (-16%) and apolipoprotein B (-16%) and with significant reductions from baseline for LDL-cholesterol (-22%), the LDL/HDL-cholesterol ratio (-13%), and the ratio of serum apolipoprotein B to apolipoprotein A-1 (-12%). Relative to placebo, mean HDL-cholesterol, total triglycerides, and apolipoprotein A-1 concentrations remained unchanged. Daily oral administration of microgram quantities of enprostil is associated with reductions in total cholesterol, LDL-cholesterol, and apolipoprotein B suggesting therapeutic potential of this synthetic prostaglandin for the treatment of hyperlipidemia.
Atherosclerosis 1988 May
PMID:Reduction of serum lipoproteins in man by the oral administration of a prostaglandin analogue (enprostil). 313 81

This study reports on 22 patients (18 men, 4 women), 45-83-year-old admitted to hospital less than 24 h after the first clinical signs of myocardial infarction. Lipids, lipoproteins, serum insulin and growth hormone, urinary cortisol and vanillylmandelic acid and blood glucose were analysed on the day of admission (day 1) and on days 2, 4 and 8 of the acute phase. Results for lipoproteins generally confirm those of earlier studies: lowered total cholesterol (day 1-8), LDL-cholesterol (day 1-2), HDL-cholesterol (day 2-8), LDL apo B (day 1-2) and apo A-1 (day 1-8). There was no significant correlation between stress hormone and plasma lipoprotein alterations. Blood glucose decreased progressively (P less than 0.05) between day 1 and day 8. Glucose value at day 1 correlated significantly with nonesterified fatty acids, total cholesterol and LDL constituents, but not with HDL-cholesterol and apo A-1. Metabolic disturbances modifying blood glucose thus might be involved in LDL changes, whereas other processes govern HDL changes.
Atherosclerosis 1988 Feb
PMID:Variations in lipoproteins, hormones and blood glucose during the early acute phase of myocardial infarction. 327 67

A total of 167 patients undergoing investigation for suspected coronary artery disease (CAD) were genotyped for restriction fragment length polymorphisms (RFLP) at the apo A-1/C-III locus and the insulin gene locus using cloned human apo A-1 and insulin gene probes. The study group was subdivided into patients with absent or minimal CAD, intermediate CAD and severe obstructive CAD. An Sst-1 polymorphism located in the 3' non-coding region of the apo C-III gene identifies two alleles. One of the alleles (S2) showed a significantly increased frequency in the subjects with severe obstructive CAD (18%) compared with patients with minimal or absent CAD (6%) (P less than 0.025) and normolipidaemic control subjects. This A-1/C-III polymorphism may be a marker for an abnormality in the A-1/C-III genes predisposing to atherosclerosis. In contrast to a previous report, we found no increase in the frequency of the Class 3 insulin alleles in subjects with severe CAD.
Atherosclerosis 1985 Dec
PMID:DNA polymorphisms in the apolipoprotein C-III and insulin genes and atherosclerosis. 391 67

The levels of apolipoproteins B, E and A-1 and the molecular species of triacylglycerols, phospholipids and cholesteryl esters were individually quantitated by electroimmunoassay and gas chromatographic total lipid profiling in 50 fresh samples of umbilical cord sera obtained from full term, normal delivery, healthy human neonates. All samples were screened for IgA to eliminate those samples with maternal blood contamination. The whole serum apolipoprotein levels in mg/dl +/- SEM for all neonates were; Apo B = 25.4 +/- 1.2; Apo E = 5.0 +/- 0.3; Apo A-1 = 86.6 +/- 2.3. These values represented 25% and 60% of adult serum values for Apo B and A-1, respectively, with normal adult values for Apo E. Apo A-1 was higher (P less than 0.020) in sera from female when compared to male neonates. The whole serum lipid values in mg/dl +/- SEM for all neonates were: 20.8 +/- 2.0 for triacylglycerols; 74.2 +/- 2.6 for lecithin and sphingomyelin; 79.8 +/- 2.7 for cholesteryl esters and 20.4 +/- 0.8 for unesterified cholesterol. Phospholipids, cholesteryl esters and total cholesterol levels were higher (P less than 0.025) in sera from female neonates when compared to males. The proportion of unesterified cholesterol relative to cholesteryl esters was high in comparison to adult sera, however the total cholesterol to phospholipid ratios were similar. The molecular species of cord sera triacylglycerols indicated a decreased proportion of C16 fatty acids with increased C18 and C20 when compared to adult sera. The molecular species of cord sera phospholipids similarly contained a decreased proportion of C16/18 fatty acids with increased C18/20 or C16/22 fatty acid combinations when compared to adults. The cord sera cholesteryl esters contained a significantly higher proportion of cholesterol esterified to C16 fatty acids with decreased amounts of cholesterol esterified to C18 and C20 fatty acids when compared to adults. Good correlations were obtained between Apo B and total serum cholesterol (R = 0.77) and also between Apo B and total serum triacylglycerols (R = 0.78).
Atherosclerosis 1984 Apr
PMID:The lipoproteins of human umbilical cord blood apolipoprotein and lipid levels. 672

Colestipol is a safe, effective, cholesterol-lowering, bile-acid sequestrant that lowers low-density-lipoprotein (LDL) and total plasma cholesterol levels without consistently affecting high-density-lipoprotein (HDL) cholesterol levels. Long-term colestipol therapy in conjunction with diet may reduce xanthoma size, arrest progression of coronary artery atherosclerosis, and may reduce mortality from coronary heart disease. Probucol, a bisphenol cholesterol-lowering drug, is an effective cholesterol-lowering agent that reduces levels of HDL cholesterol, HDL cholesterol, and apoprotein A-1, the major apolipoprotein of HDL. Because HDL cholesterol is independently and inversely associated with development of coronary heart disease, the ramifications of simultaneous lowering of LDL and HDL cholesterol levels by probucol treatment need further study. Long-term, placebo-controlled studies of repetitive coronary arteriography, coronary heart disease morbidity and mortality, or both are needed to ascertain the efficacy of long-term probucol use in relation to development of atherosclerosis.
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PMID:Colestipol and probucol: treatment of primary and familial hypercholesterolemia and amelioration of atherosclerosis. 703 45

The high density lipoprotein HDL) response of 14 hyperlipidemic subjects to four hypolipidemic agents was studied through serial measurement of HDL cholesterol and apolipoproteins A-I and A-II before and during 3 months each (separated by 2 months off drug) of clofibrate (2 g/day, n = 14), colestipol (20 g/day, n = 12), para-amino salicylic acid--ascorbate (PAS-C, 6--8 g/day, n = 14) taken in random sequence and oxandrolone (7.5 mg/day, n = 11) as the final drug. The maximal effect of each drug appeared by the first monthly evaluation, and A-1, A-II and HDL cholesterol levels returned to pretreatment levels by one month after discontinuation of each agent. With clofibrate, HDL cholesterol increased by 16 +/- 20% from baseline (mean +/- SD) (P less than 0.05), A-I by 11 +/- 13% (P less than 0.05) and A-II by 39 +/- 17% (P less than 0.01). During oxandrolone HDL cholesterol declined by 36 +/- 20% from baseline (P less than 0.01), A-I by 21 +/- 13% (P less than 0.01), and A-II by 16 +/- 11% (P less than 0.025). Neither PAS-C nor colestipol exerted major effects on HDL, or any of the variables although both were associated with a slight rise in the A-I/A-II ratio (11 +/- 15% and 12 +/- 12%, respectively).
Atherosclerosis 1980 Mar
PMID:High density lipoproteins during hypolipidemic therapy. A comparative study of four drugs. 736 96

Human serum paraoxonase is physically associated with HDL and has been implicated in the detoxification of organophosphates and possibly in the prevention of LDL lipid peroxidation. We investigated the serum activity and concentration of paraoxonase in 78 patients with type 1 diabetes mellitus, 92 with type 2 diabetes, and 82 nondiabetic control subjects. Paraoxonase activity was generally lower in diabetics than in control subjects. This decrease was unrelated to differences in paraoxonase phenotype distribution or its serum concentration. Rather, the difference in paraoxonase activity was explained by its specific activity, which was lower in diabetics, indicating either the presence of a circulating inhibitor or disturbance of the interaction of paraoxonase with HDL affecting its activity. Paraoxonase specific activity was lowest in patients with peripheral neuropathy, suggesting an association of paraoxonase with neuropathy. In control subjects but not patients with diabetes, paraoxonase correlated with HDL cholesterol and apolipoprotein A-1. Our results indicate that the low paraoxonase activity in diabetes is due to decreased specific activity. In other studies low serum paraoxonase activity has been associated with increased susceptibility to atherosclerosis, and the present results also suggest an association with peripheral neuropathy, which could be due to reduced capacity to detoxify lipid peroxides in diabetes.
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PMID:Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins. 758 60

Agents that inhibit hepatic cholesterol biosynthesis reduce circulating cholesterol levels in experimental animals and humans, and may be of pharmacological importance in the prevention of atherosclerosis. Azalanstat (RS-21607), a synthetic imidazole, has been shown to inhibit cholesterol synthesis in HepG2 cells, human fibroblasts, hamster hepatocytes and hamster liver, by inhibiting the cytochrome P450 enzyme lanosterol 14 alpha-demethylase. When administered orally to hamsters fed regular chow, RS-21607 (50 mg/kg/day) lowered serum cholesterol in a dose-dependent manner (ED50 = 62 mg/kg) in a period of 1 week. It preferentially lowered low density lipoprotein (LDL) cholesterol and apo B relative to high density lipoprotein (HDL) cholesterol and apo A-1. It also lowered plasma cholesterol levels in hamsters fed a high saturated fat and cholesterol diet. RS-21607 inhibited hepatic microsomal hydroxymethylglutaryl-CoA (HMG-CoA) reductase activity in hamsters in a dose-dependent manner (ED50 = 31 mg/kg), and this was highly correlated with serum cholesterol lowering (r = 0.97). Cholesterol lowering by azalanstat and cholestyramine was additive, and the increase in HMG-CoA reductase brought about by cholestyramine was attenuated significantly by azalanstat. In vitro studies with HepG2 cells indicated that this modulation of reductase activity was indirect, occurring at a post-transcriptional step, and it is proposed that a regulatory oxysterol derived from dihydrolanosterol (or lanosterol) may be responsible for this regulation. Azalanstat does not appear to lower circulating cholesterol in the hamster by up-regulation of the hepatic LDL receptor, suggesting that other mechanisms are involved. Orally administered azalanstat (50-75 mg/kg) stimulated hepatic microsomal cholesterol 7 alpha-hydroxylase activity by 50-400% in hamsters, and it is postulated that this may result from modified cholesterol absorption and bile acid synthesis.
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PMID:Azalanstat (RS-21607), a lanosterol 14 alpha-demethylase inhibitor with cholesterol-lowering activity. 764 60

The study covered peculiarities of lipid metabolism in workers engaged into lead production. Most the examinees showed reliable increase of total blood cholesterol, low and extremely low density lipoproteins cholesterol, triglycerides and atherogenic coefficient, combined with decreased high density lipoproteins cholesterol. Occupational factor was proved dominant in atherosclerosis formation in lead production workers. Those workers demonstrated also significant comedown of Apo A-1 amount, reliable increase of Apo B level and Apo B/Apo A-1 ratio.
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PMID:[Characteristics of the serum lipids in workers of lead industry]. 771 52


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