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)

Peroxisome proliferator-activated receptors (PPARs) and liver X receptor alpha are ligand-activated transcription factors that belong to nuclear receptors superfamily and are involved in the regulation of lipid metabolism. PPAR, especially PPAR-alpha, PPAR-gamma agonists and liver X receptor alpha agonists can regulate the expression or biosynthesis of some factors involved in the formation and function of HDL, such as apolipoprotein (apo) A-I and ATP binding cassette transporter A1 (ABCA1). It is well known that HDL plays an important role in the treatment of hyperlipidemia as the carrier of reverse cholesterol transport. In the present study, the anti-hyperlipidemic properties of CM108, a derivative of flavone, 9-Hydroxy-2-mercapto-6-phenyl-2-thioxo-1,3,5-trioxa-2lambda(5)-phospha-cyclopenta[b]naphthalen-8-one, were studied. Through the transactivation assays of in vitro study, it was discovered that CM108 could activate PPAR-alpha PPAR-gamma and liver X receptor alpha at 40-150 microg/ml, which subsequently resulted in activating ABCA1 promoter and enhancing apoA-I and apoA-II production, whereas reducing apoC-III production significantly. Furthermore, after in vivo study that the hyperlipidemic rats were treated with CM108 for 4 weeks, a significant increase was found in HDL cholesterol levels (26.7%, P<0.05) and a significant decrease was also noticed in triglyceride levels (26.3%, P<0.01) at 100 mg/kg CM108 group compared with that of control animals. Meanwhile, the atherogenicity index, represented by total cholesterol/HDL ratio, was significantly reduced (P<0.01). In conclusion, CM108 can effectively elevate HDL levels and lower triglyceride levels in hyperlipidemic rats maybe by regulating a series of genes, receptors and proteins related to HDL.
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PMID:Anti-hyperlipidemic properties of CM108 (a flavone derivative) in vitro and in vivo. 1702 88

Lipid and cholesterol metabolism in the postprandial phase is associated with both quantitative and qualitative remodeling of HDL particle subspecies that may influence their anti-atherogenic functions in the reverse cholesterol transport pathway. We evaluated the capacity of whole plasma or isolated HDL particles to mediate cellular free cholesterol (FC) efflux, cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester (CE) transfer, and selective hepatic CE uptake during the postprandial phase in subjects displaying type IIB hyperlipidemia (n = 16). Postprandial, large HDL2 displayed an enhanced capacity to mediate FC efflux via both scavenger receptor class B type I (SR-BI)-dependent (+12%; P < 0.02) and ATP binding cassette transporter G1 (ABCG1)-dependent (+31%; P < 0.008) pathways in in vitro cell systems. In addition, the capacity of whole postprandial plasma (4 h and 8 h postprandially) to mediate cellular FC efflux via the ABCA1-dependent pathway was significantly increased (+19%; P < 0.0003). Concomitantly, postprandial lipemia was associated with elevated endogenous CE transfer rates from HDL2 to apoB lipoproteins and with attenuated capacity (-17%; P < 0.02) of total HDL to deliver CE to hepatic cells. Postprandial lipemia enhanced SR-BI and ABCG1-dependent efflux to large HDL2 particles. However, postprandial lipemia is equally associated with deleterious features by enhancing formation of CE-enriched, triglyceride-rich lipoprotein particles through the action of CETP and by reducing the direct return of HDL-CE to the liver.
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PMID:Postprandial lipemia enhances the capacity of large HDL2 particles to mediate free cholesterol efflux via SR-BI and ABCG1 pathways in type IIB hyperlipidemia. 2071 50

Hyperlipidemia is one of the most important risk factors for atherosclerosis, coronary heart disease and other cardiovascular diseases. It is the main effect of lipid-lowering drugs to reduce the plasma low-density lipoprotein or to enhance high-density lipoprotein. Niemann-Pick C1 like 1 protein (NPC1L1), acyl-coenzyme A: cholesterol acyltransferases (ACAT), ATP binding cassette transporter G member 5 and member 8 (ABCG5/G8), microsomal triglyceride transfer protein (MTP), monoacylglycerol acyltransferase, diacylglycerol acyltransferases (MAGT), peroxisome proliferator-activated receptor (PPAR), farnesoid X receptor (FXR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) play key roles in the metabolism of lipid, which are regarded as the targets of anti-hyperlipidemia drugs and evidence for clinic choice of lipid-lowering drugs. These proteins are considered as breakthrough points for new lipid-lowering drug development.
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PMID:[Targets of anti-hyperlipidemia drugs]. 2340 52

Although antiretroviral therapy (ART) has resulted in a marked decrease in AIDS-related morbidity and mortality, the therapeutic benefit is often limited by side effects such as metabolic derangement such as lipodystrophy and hyperlipidemia and cardiovascular diseases. These side effects are pervasive in people living with HIV (PLWH). However, the underlying mechanisms are not completely understood. We investigated the effects of ART on cholesterol biosynthesis genes. This is a retrospective analysis of data and specimens collected during a cross-sectional, case-control study of ART-induced toxicity. Cases were HIV treatment-experienced individuals with HIV viral suppression and no diagnosis of ART-associated toxicity (n = 18), and controls were HIV-uninfected individuals (n = 18). The mRNA expressions of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and ATP binding cassette transporter A1 (ABCA1) were significantly upregulated in cases (HIV+) compared to controls (HIV-), as well as the corresponding protein expression level of HMGCR. We observed dysregulation between sterol regulatory element-binding protein 2 (SREBP-2, sensory control) and HMGCR and low-density lipoprotein receptor (LDLR) pathways. Dysregulation of cholesterol biosynthesis genes may predate clinical manifestation of ART-induced lipid abnormalities.
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PMID:Dysregulation of sterol regulatory element-binding protein 2 gene in HIV treatment-experienced individuals. 3184 98