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)

Candidate gene polymorphisms related to inflammation, thrombosis and lipid metabolism have been implicated in the development of ischemic stroke. Using DNA samples collected at baseline in a prospective cohort of 14 916 initially healthy American men, we genotyped 92 polymorphisms from 56 candidate genes among 319 individuals who subsequently developed ischemic stroke and among 2092 individuals who remained free of reported cardiovascular disease over a mean follow-up period of 13.2 years to prospectively determine whether candidate gene polymorphisms contribute to stroke risk. After adjustment for multiple comparisons and age, smoking, body mass index, hypertension, hyperlipidemia and diabetes, two related to inflammation [a val640leu polymorphism in the P-selectin gene (OR=1.63, 95% CI 1.22-2.17, P=0.001) and a C582T polymorphism in the interleukin-4 gene (OR=1.40, 95% CI 1.13-1.73, P=0.003)] were found to be independent predictors of thrombo-embolic stroke. In bootstrap replications, the inclusion of genetic information from these two polymorphisms improved prediction models for stroke based upon traditional risk factors alone (ROC 0.67 versus 0.64). Two polymorphisms related to thrombosis (an arg353gln polymorphism in the factor VII gene and a T11053G polymorphism in the plasminogen activator inhibitor type-1 gene) and one related to lipid metabolism [a C(-482)T polymorphism in the apolipoprotein CIII gene] achieved nominal significance, but were not found to be independent predictors after multiple comparison adjustment. Two inflammatory candidate gene polymorphisms were identified which were independently associated with incident stroke. These population-based data demonstrate the ability of prospective, epidemiological studies to test candidate gene associations for athero-thrombotic disease.
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PMID:Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke: a population-based, prospective genetic analysis. 1468 4

One response of the brain to stressors is to increase microglial activation with the consequent production of proinflammatory cytokines like interleukin-1beta (IL-1beta), which has been shown to exert an inhibitory effect on long-term potentiation (LTP) in the hippocampus. It has been consistently shown, particularly in vitro, that amyloid-beta (Abeta) peptides increase activation of microglia, while its inhibitory effect on LTP is well documented, and associated with the Abeta-induced increase in IL-1beta. Here we set out to establish whether the Abeta-induced inhibition of LTP in perforant path-granule cell synapses, was coupled with evidence of microglial activation and to assess whether atorvastatin, which is used primarily in the treatment of hyperlipidaemia but which possesses anti-inflammatory properties, might modulate the effect of Abeta on LTP. We report that intracerebroventricular injection of Abeta increased expression of several markers of microglial activation, and in parallel, inhibited LTP in dentate gyrus. The data show that atorvastatin abrogated the Abeta-induced microglial activation and the associated deficit in LTP. On the basis of the evidence presented, we propose that the action of atorvastatin is mediated by its ability to increase production of the anti-inflammatory cytokine, interleukin-4, which we report mimics several of the actions of atorvastatin in the rat hippocampus.
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PMID:The HMG-CoA reductase inhibitor, atorvastatin, attenuates the effects of acute administration of amyloid-beta1-42 in the rat hippocampus in vivo. 1692 Jan 63

Three-hydroxy-3-methylglutaryl CoA reductase inhibitors, also known as statins, are widely used as the drug of choice for the treatment of hyperlipidemia. However, actions beyond that of simply lowering cholesterol levels have been reported. This study aims at evaluating the effect of atorvastatin on antibody interleukin-4 and gamma-interferon production in mice immunized with egg albumin. Antibody levels were determined by an enzyme linked immunosorbent assay and cytokine transcripts by reverse transcriptase-polymerase chain reaction. Results indicated that repeated daily doses of 40 mg/Kg body weight of atorvastatin following immunization suppressed the antibody response in mice to egg albumin. Moreover, a decline in interleukin-4 and gamma-interferon transcripts was observed.
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PMID:Effect of atorvastatin on antibody, interleukin-4 and gamma-interferon production in mice immunized with egg albumin. 1699 94

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates expression of low-density lipoprotein (LDL) receptors via receptor internalization and subsequent lysosomal degradation. Thus, an anti-PCSK9 antibody is well known as an anti-hyperlipidemia drug. Here, we aimed to develop vaccine for a long-term treatment of dyslipidemia targeted to PCSK9. In This study, we designed a peptide vaccine for mouse PCSK-9, which consisted of short peptides conjugated to keyhole limpet hemocyanin (KLH) as a carrier protein. Vaccines were administered to male apolipoprotein E (ApoE) deficient mice with adjuvants and significantly elicited an antibody response against PCSK9. The PCSK9 vaccines were administered to mice three times in 2-week intervals, and antibody titers and lipoprotein levels were evaluated up to 24 weeks after the first immunization to determine the therapeutic effect. Anti-PCSK9 antibody titers reached peak levels 6 weeks after the first immunization, and theses titers were maintained for up to 24 weeks. Decreased plasma levels of total cholesterol, very low-density lipoprotein (VLDL), and chylomicron (CM) were maintained for up to 24 weeks. Immunized mice exhibited a significant increase in cell-surface LDL receptor expression. Stimulation with KLH, but not PCSK9, induced the production of INF-gamma and interleukin-4 (IL-4), as determined with ELISPOT assays, thus indicating that PCSK9 vaccine did not elicit T-cell activation in our vaccine system. The present anti-PCSK9 vaccine induced long-lasting anti-PCSK9 antibody production and improved lipoprotein profiles. Thus, anti-PCSK9 vaccine could become a new option for the treatment of dyslipidemia as a long-acting therapy in future.
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PMID:Development of vaccine for dyslipidemia targeted to a proprotein convertase subtilisin/kexin type 9 (PCSK9) epitope in mice. 2943 41