FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3107560778> ?p ?o ?g. }

• W3107560778 endingPage "934" @default.
• W3107560778 startingPage "921" @default.
• W3107560778 abstract "The high-density lipoprotein hypothesis of atherosclerosis has been challenged by clinical trials of cholesteryl ester transfer protein (CETP) inhibitors, which failed to show significant reductions in cardiovascular events. Plasma levels of high-density lipoprotein cholesterol (HDL-C) decline drastically during sepsis, and this phenomenon is explained, in part, by the activity of CETP, a major determinant of plasma HDL-C levels. We tested the hypothesis that genetic or pharmacological inhibition of CETP would preserve high-density lipoprotein levels and decrease mortality in clinical cohorts and animal models of sepsis.We examined the effect of a gain-of-function variant in CETP (rs1800777, p.Arg468Gln) and a genetic score for decreased CETP function on 28-day sepsis survival using Cox proportional hazard models adjusted for age and sex in the UK Biobank (n=5949), iSPAAR (Identification of SNPs Predisposing to Altered Acute Lung Injury Risk; n=882), Copenhagen General Population Study (n=2068), Copenhagen City Heart Study (n=493), Early Infection (n=200), St Paul's Intensive Care Unit 2 (n=203), and Vasopressin Versus Norepinephrine Infusion in Patients With Septic Shock studies (n=632). We then studied the effect of the CETP inhibitor, anacetrapib, in adult female APOE*3-Leiden mice with or without human CETP expression using the cecal-ligation and puncture model of sepsis.A fixed-effect meta-analysis of all 7 cohorts found that the CETP gain-of-function variant was significantly associated with increased risk of acute sepsis mortality (hazard ratio, 1.44 [95% CI, 1.22-1.70]; P<0.0001). In addition, a genetic score for decreased CETP function was associated with significantly decreased sepsis mortality in the UK Biobank (hazard ratio, 0.77 [95% CI, 0.59-1.00] per 1 mmol/L increase in HDL-C) and iSPAAR cohorts (hazard ratio, 0.60 [95% CI, 0.37-0.98] per 1 mmol/L increase in HDL-C). APOE*3-Leiden.CETP mice treated with anacetrapib had preserved levels of HDL-C and apolipoprotein-AI and increased survival relative to placebo treatment (70.6% versus 35.3%, Log-rank P=0.03), whereas there was no effect of anacetrapib on the survival of APOE*3-Leiden mice that did not express CETP (50.0% versus 42.9%, Log-rank P=0.87).Clinical genetics and humanized mouse models suggest that inhibiting CETP may preserve high-density lipoprotein levels and improve outcomes for individuals with sepsis." @default.
• W3107560778 created "2020-12-07" @default.
• W3107560778 creator A5002813307 @default.
• W3107560778 creator A5005991594 @default.
• W3107560778 creator A5010687095 @default.
• W3107560778 creator A5012378798 @default.
• W3107560778 creator A5016373252 @default.
• W3107560778 creator A5022615366 @default.
• W3107560778 creator A5025213353 @default.
• W3107560778 creator A5029200964 @default.
• W3107560778 creator A5030267591 @default.
• W3107560778 creator A5035385427 @default.
• W3107560778 creator A5056253730 @default.
• W3107560778 creator A5057412949 @default.
• W3107560778 creator A5064696998 @default.
• W3107560778 creator A5067391389 @default.
• W3107560778 creator A5079728437 @default.
• W3107560778 creator A5090576091 @default.
• W3107560778 date "2021-03-02" @default.
• W3107560778 modified "2023-10-18" @default.
• W3107560778 title "Inhibition of Cholesteryl Ester Transfer Protein Preserves High-Density Lipoprotein Cholesterol and Improves Survival in Sepsis" @default.
• W3107560778 cites W1626021976 @default.
• W3107560778 cites W1990237691 @default.
• W3107560778 cites W1997140310 @default.
• W3107560778 cites W2018795125 @default.
• W3107560778 cites W2020361370 @default.
• W3107560778 cites W2027430472 @default.
• W3107560778 cites W2037587089 @default.
• W3107560778 cites W2048760408 @default.
• W3107560778 cites W2050066090 @default.
• W3107560778 cites W2055729264 @default.
• W3107560778 cites W2062206062 @default.
• W3107560778 cites W2073999834 @default.
• W3107560778 cites W2087203965 @default.
• W3107560778 cites W2087817212 @default.
• W3107560778 cites W2096137537 @default.
• W3107560778 cites W2108153775 @default.
• W3107560778 cites W2118825330 @default.
• W3107560778 cites W2128929628 @default.
• W3107560778 cites W2129941946 @default.
• W3107560778 cites W2132328792 @default.
• W3107560778 cites W2132607058 @default.
• W3107560778 cites W2134811220 @default.
• W3107560778 cites W2137113092 @default.
• W3107560778 cites W2142113371 @default.
• W3107560778 cites W2145221987 @default.
• W3107560778 cites W2147108549 @default.
• W3107560778 cites W2153118028 @default.
• W3107560778 cites W2156689595 @default.
• W3107560778 cites W2158092179 @default.
• W3107560778 cites W2161241326 @default.
• W3107560778 cites W2167320417 @default.
• W3107560778 cites W2169943839 @default.
• W3107560778 cites W2173669545 @default.
• W3107560778 cites W2219591537 @default.
• W3107560778 cites W2280404143 @default.
• W3107560778 cites W2383906058 @default.
• W3107560778 cites W2510973425 @default.
• W3107560778 cites W2518489812 @default.
• W3107560778 cites W2555385098 @default.
• W3107560778 cites W2560002818 @default.
• W3107560778 cites W2596126968 @default.
• W3107560778 cites W2614741637 @default.
• W3107560778 cites W2616536890 @default.
• W3107560778 cites W2616744155 @default.
• W3107560778 cites W2617291249 @default.
• W3107560778 cites W2623413084 @default.
• W3107560778 cites W2749237115 @default.
• W3107560778 cites W2762777606 @default.
• W3107560778 cites W2775150242 @default.
• W3107560778 cites W2793835122 @default.
• W3107560778 cites W2800588134 @default.
• W3107560778 cites W2884162456 @default.
• W3107560778 cites W2884966596 @default.
• W3107560778 cites W2887296216 @default.
• W3107560778 cites W2895486342 @default.
• W3107560778 cites W2896434545 @default.
• W3107560778 cites W2897553891 @default.
• W3107560778 cites W2899710052 @default.
• W3107560778 cites W2900719300 @default.
• W3107560778 cites W2901788545 @default.
• W3107560778 cites W2978943916 @default.
• W3107560778 cites W2988851086 @default.
• W3107560778 cites W2998853022 @default.
• W3107560778 cites W3016555942 @default.
• W3107560778 cites W3063828557 @default.
• W3107560778 cites W4246011285 @default.
• W3107560778 doi "https://doi.org/10.1161/circulationaha.120.048568" @default.
• W3107560778 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33228395" @default.
• W3107560778 hasPublicationYear "2021" @default.
• W3107560778 type Work @default.
• W3107560778 sameAs 3107560778 @default.
• W3107560778 citedByCount "46" @default.
• W3107560778 countsByYear W31075607782021 @default.
• W3107560778 countsByYear W31075607782022 @default.
• W3107560778 countsByYear W31075607782023 @default.
• W3107560778 crossrefType "journal-article" @default.
• W3107560778 hasAuthorship W3107560778A5002813307 @default.

• next