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)

HyperapoB, a lipoprotein phenotype characterized by increased numbers of small, dense, low-density lipoproteins (LDL), is strongly associated with coronary artery disease (CAD). Patients with hyperapoB may be normolipidemic, hypertriglyceridemic, or, when the number of LDL particles increases sufficiently, hypercholesterolemic. Concentrations of high-density lipoprotein (HDL) and its major apolipoprotein, apo A-1, are often low in plasma of patients with hyperapoB. The increased number of dense LDL in hyperapoB is due to increased LDL synthesis, secondary to increased synthesis of very-low-density lipoproteins (VLDL) and apo B. HyperapoB may be a dominant trait, although the existence of a common recessive allele at a very high frequency has not been excluded. The expression of hyperapoB appears delayed, but the phenotype is commonly found in children referred to specialty lipid clinics because of a family history of premature CAD. Published data suggest a biochemical, genetic, and metabolic relationship between hyperapoB, familial combined hyperlipidemia, and the dense LDL subclass patterns described in Mormon families. The biochemical and genetic basis for the overproduction of VLDL apo B is under further study, both molecular investigations of the apo B gene and studies of free fatty acid, triglyceride, and HDL metabolism.
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PMID:HyperapoB: a pleiotropic phenotype characterized by dense low-density lipoproteins and associated with coronary artery disease. 304 2

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.
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PMID:Reduction of serum lipoproteins in man by the oral administration of a prostaglandin analogue (enprostil). 313 81

Two gene specific probes have been used to identify polymorphic DNA loci on chromosome 11 close to the insulin and apoprotein A-1 genes in a genetic analysis of hypertriglyceridaemic patients with and without co-existing diabetes. Of the 45 patients studied with both probes, 15 were diabetic of whom nine possessed class 3/3 insulin polymorphism genotypes, compared with none in the non-diabetic group (p less than 0.001; chi 2 test). In contrast, an uncommon apolipoprotein A-1 polymorphism was found to be equally distributed in the diabetic and the non-diabetic patients. No co-segregation of these two particular genetic polymorphisms was found in either patient group. The differing associations of the two disease-related polymorphism genotypes in patients with hypertriglyceridaemia with or without co-existing diabetes may possibly reflect differing aetiologies of the hyperlipidaemia.
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PMID:Insulin and apolipoprotein A-1/C-III gene polymorphisms relating to hypertriglyceridaemia and diabetes mellitus. 643 27

Arginine decreased cholesterol and triglyceride content in blood sera of intact rats and inhibited the development of hyperlipidemia provoked by Triton WR-1339 injection. In rabbits pretreated with cholesterol arginine diminished the content of blood serum cholesterol and triglycerides. Introduction of arginine to intact and hyperlipidemic guinea pigs decreased the VLDL and increased the HDL level. Under influence of arginine electrophoretic zone of HDL apo A-1 was more pronounced and apo E zone became less distinct in hyperlipidemic guinea pigs.
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PMID:[Effect of arginine on the lipid and lipoprotein content of animal blood]. 652 39

Hyperlipidemia is common in renal allograft recipients. To elucidate the role of cyclosporine in posttransplant hyperlipidemia, we measured lipids, lipoprotein lipids, and apolipoproteins of thirty-five renal allograft recipients and evaluated their relation to trough cyclosporine blood levels. All patients were on a triple immunosuppressive regimen with equal doses of prednisone and azathioprine, and had stable graft function. Cyclosporine blood levels were significantly correlated to total plasma cholesterol (P = 0.028), low-density lipoprotein cholesterol (P = 0.022), apolipoprotein B (P = 0.017), and the cholesterol/high-density lipoprotein cholesterol ratio (P < 0.002), but not to plasma triglycerides. Significant inverse correlations were found between cyclosporine blood levels and high-density lipoprotein cholesterol (P = 0.034), high-density lipoprotein3 cholesterol (P = 0.025), and apolipoprotein A-1 (P = 0.047), but not high-density lipoprotein2 cholesterol. The independent relation of cyclosporine blood levels to each of the measured lipid parameters was investigated by a stepwise regression model including age, body mass index, interval from transplantation, diabetes mellitus, plasma creatinine, and intake of diuretics and beta-blockers. After correction for these 7 variables, cyclosporine blood levels remained significantly associated with high-density lipoprotein cholesterol, high-density lipoprotein3 cholesterol, apolipoprotein A-1, apolipoprotein B, low-density lipoprotein cholesterol, and the cholesterol/high-density lipoprotein cholesterol ratio. These data suggest that cyclosporine causes atherogenic dyslipidemia.
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PMID:Relation of cyclosporine blood levels to adverse effects on lipoproteins. 819 11

Alcohol intake and exercise have both been found to be related to increased plasma levels of high density lipoprotein cholesterol (HDLC). Exercise training results in decreased postprandial lipemia, and clearance rate of infused lipids is related to plasma lipoprotein levels in physically active men. The effect of alcohol intake on plasma triglyceride (TG) clearance has not been studied in relation to the exercise status of subjects. Plasma TG change over 8 h was determined following a liquid fatty meal in 14 male habitual runners (R) and 13 physically inactive men (I) after 3 weeks of alcohol abstinence and 3 weeks of drinking approximately 41 g (1.44 oz) of ethanol per day. Fasting total cholesterol and apolipoprotein A-1 (apo A-1) were not different between groups, but TG was lower and HDLC, HDL2C, and HDL3C were higher in the runners. After abstinence, I had slower TG clearance (P = 0.07) compared with R; with alcohol, TG clearance was unchanged in R, but was significantly retarded in I. With alcohol, both groups had increased HDLC levels, but this mainly was due to an increase in HDL3C in R and HDL2C in I; apo A-1 increased similarly in both groups and fasting TG increased significantly only in I. Alcohol-induced increases in postprandial lipemia and retardation of TG clearance appear to occur in inactive, but not exercise-trained subjects and the effect of alcohol on plasma HDL subfractions may differ between these groups.
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PMID:Effect of alcohol and exercise on postprandial lipemia and triglyceride clearance in men. 831 61

Rats treated with puromycin aminonucleoside (PAN) developed characteristics of the nephrotic syndrome, including albuminuria, hypoalbuminemia and hyperlipidemia. To study the regulation of apolipoprotein (apo) A-1 and apo E gene expression in nephrotic rats, we analyzed the steady-state levels (SSLs) of hepatic and intestinal apo A-1 and apo E mRNA using the Northern technique, and the plasma levels of high-density lipoprotein (HDL) by biochemical methods. Male Wistar rats were treated with PAN and compared with pair-fed and untreated control rats at different stages of disease. Nephrotic rats presented with marked hypoalbuminemia and albuminuria at between 6 and 11 days after PAN treatment. During this stage of disease, plasma levels of HDL were elevated in correlation with an increase of both hepatic and intestinal apo A-1 mRNA. In liver of nephrotic rats, high levels of apo A-1 mRNA together with low levels of apo E mRNA caused an increase in the ratio of apo A-1/apo E mRNA, reaching a maximum 6 days after treatment. Apo E mRNA was barely detected in small intestine of pair-fed controls and PAN-treated rats. However, contrary to nephrotic rats, the ratio apo A-1/apo E mRNA was inverted in liver of pair-fed rats due to an increase in apo E mRNA. In conclusion, in nephrotic rats, the SSL of apo A-1 mRNA is increased in liver and small intestine and appears to regulate the plasma levels of apo A-1. These results also suggest a coordinated regulation of the apo A-1 and apo E gene expression in liver of nephrotic and pair-fed rats.
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PMID:Regulation of apolipoprotein A-1 and E gene expression in liver and intestine of nephrotic and pair-fed rats. 841 67

In experimental nephrosis, a decrease in plasma albumin resulting from proteinuria causes a decreased in the plasma oncotic pressure. The existence of an osmoreceptor, which responds to the low oncotic pressure and produces a factor(s) that signals the liver to increase the secretion of plasma proteins, is postulated. The hyperlipidemia characteristic of the nephrotic syndrome results primarily from increased hepatic secretion of apolipoproteins and lipoproteins representing the entire density spectrum from VLDL, IDL, and LDL to HDL. Not all plasma proteins and apolipoproteins are affected to the same extent. Increased mRNA levels due to increased transcription have been shown for albumin and apolipoprotein A-1 (apoA-1). The increased secretion of VLDL, the major vehicle for triglyceride transport from the liver, appears to be due mainly to posttranscriptional events possibly related to increased lipogenesis. Once proteinuria begins, the demand for amino acids for albumin and apolipoprotein synthesis by the liver is increased. To meet this demand, protein catabolism in the peripheral tissues is increased. One manifestation of this process is a decrease in lipoprotein lipase which reduces VLDL catabolism, contributing to the sustained elevation of plasma VLDL. The spectacular overproduction of apoA-1 in nephrosis in the rat is accompanied by a decreased fractional catabolic rate (FCR), contributing to the maintenance of high levels of HDL. Urinary loss of HDL and its renal catabolism does not account for the decreased FCR. The reason for the decreased FCR is not known. Work with nephrotic rats overexpressing transgenic human apoA-1 has shown that human A-1 forms smaller HDL3-sized particles, rather than the larger HDL2 of the rat. This may contribute to the failure of HDL levels to increase in the human nephrotic syndrome. High plasma VLDL and LDL with normal or low HDL probably account for the increased incidence of coronary artery disease in the nephrotic syndrome.
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PMID:Lipoprotein metabolism in experimental nephrosis. 893 62

This study analyzes the relationship of plasmatic colloid osmotic pressure (PCO) and viscosity with the different hyperlipidemic stages observed in rats with acute liver damage induced by carbon tetrachloride (CCl4) and in rats with nephrotic syndrome induced by puromycin amino nucleoside (PAN). In both animal models viscosity increases were associated with the induction of the hyperlipidemic stage characterized by an increase of high density lipoproteins (HDL) and steady-state levels (SSL) of apo A-1 mRNA. In both animal models PCO decreased at early stages of the disease when hyperlipidemia was characterized principally by an increase of total cholesterol and triacylglycerols, but was not associated with the induction of HDL and apo A-1 mRNA. To confirm the in vivo findings, we studied the effect of viscosity on apo A-1 gene expression in an in vitro model using cultured hepatocytes. When medium viscosity was maintained below physiological values, an induction of the SSL of apo A-1 mRNA was observed. By contrast, when medium viscosity was raised to values similar or higher than the physiological range, the SSL of apo A-1 mRNA decreased steadily and after 24 h incubation an almost total inhibition was observed. These results suggest that in both experimental animal models of secondary hyperlipidemia, small viscosity changes below the physiological range, most probably in the interstitial fluid, can induce apo A-1 gene expression at the mRNA level, and that when viscosity reaches physiological values, apo A-1 gene expression is inhibited. Both effects were shown in cultured hepatocytes.
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PMID:Viscosity regulates apolipoprotein A-1 gene expression in experimental models of secondary hyperlipidemia and in cultured hepatocytes. 905 16

Evidence was provided that atherogenesis develops for several decades before pathological changes are manifested. It may thus be stated, that the "incubation period" of atherosclerotic pathological consequences is very long but it is reduced markedly already from childhood and adolescence in subjects with an atherogenic lipoprotein phenotype. Atherogenic lipoprotein phenotype comprises subjects suffering from one or more, frequently from a combination of several of the following metabolic indicators: hypercholesterolaemia, elevated levels of LDL-cholesterol, apolipoprotein B, lipoprotein (a), reduced levels of HDL-cholesterol and apolipoprotein A-1. The atherogenic lipoprotein phenotype is in 95% conditioned by inborn metabolic errors, i.e. familial hyperlipoproteinaemia and dyslipoproteinaemia. In the population the following are encountered most frequently: combined familial hyperlipidaemia, familial hypertriacylglycerolaemia and familial hypercholesterolaemia. Active screening and treatment of children and adolescents from these affected families is of great importance in primary prevention of atherosclerotic complications in adult age.
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PMID:[Screening and treatment of children and adolescents with hypercholesterolemias and dyslipidemias]. 951 Dec 74


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