MARC Record from marc_columbia

LEADER: 02721cam a22003973i 4500
001 14840860
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006 m o d
007 cr |n||||a||||
008 200428s2019 nyu|||| om 00| ||eng d
035 $a(OCoLC)1090211568
035 $a(OCoLC)on1090211568
035 $a(NNC)ACfeed:legacy_id:ac:kd51c5b008
035 $a(NNC)ACfeed:doi:10.7916/d8-5wc2-4f04
035 $a(NNC)14840860
040 $aNNC$beng$erda$cNNC
100 1 $aThomas, David George.
245 10 $aLiver X Receptor cis-Repression and Cholesterol Efflux Restrain Innate Immunity and Coronary Artery Disease /$cDavid George Thomas.
264 1 $a[New York, N.Y.?] :$b[publisher not identified],$c2019.
336 $atext$btxt$2rdacontent
337 $acomputer$bc$2rdamedia
338 $aonline resource$bcr$2rdacarrier
300 $a1 online resource.
502 $aThesis (Ph.D.)--Columbia University, 2019.
500 $aDepartment: Cellular, Molecular and Biomedical Studies.
500 $aThesis advisor: Alan R. Tall.
520 $aAtherosclerotic cardiovascular disease secondary to deposition of apolipoprotein B-containing lipoproteins in the artery wall is a leading cause of mortality. Therapies that reduce serum levels of atherogenic lipoprotein-cholesterol have been successful in reducing cardiovascular mortality, but this approach requires long-term treatment and substantial residual risk remains. Here, we investigate mechanistic determinants of atherosclerosis protection by two potential therapeutic approaches for lowering of residual cardiovascular risk. Using mouse models, we show that the nuclear receptor liver X receptor exerts an anti-inflammatory activity on innate immunity and atherosclerosis through both promotion of cholesterol efflux and a direct cis-repressive activity affecting neutrophil inflammation. We then assess the causal role of the cholesterol efflux pathway in human cardiovascular events by using genetic variants that modify high density lipoprotein-cholesterol in instrumental variable analysis.
520 $aWe show that this pathway is associated with protection from cardiovascular disease in a precise and robust Mendelian randomization analysis on an FDR-controlled set of variants, which suggests a causal effect. Thus, agents that target the cholesterol efflux and liver X receptor cis-repression pathways may be protective in atherosclerosis.
653 0 $aCytology
653 0 $aMolecular biology
653 0 $aBiochemistry
653 0 $aAtherosclerosis--Prevention
653 0 $aImmunity
653 0 $aNuclear receptors (Biochemistry)
856 40 $uhttps://doi.org/10.7916/d8-5wc2-4f04$zClick for full text
852 8 $blweb$hDISSERTATIONS