About: Genetic control of the mouse HDL proteome defines HDL traits, function, and heterogeneity

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About: Genetic control of the mouse HDL proteome defines HDL traits, function, and heterogeneity Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Genetic control of the mouse HDL proteome defines HDL traits, function, and heterogeneity
Creator	Heinecke, J Hutchins, P Irwin, A Lusis, A Pan, C Plubell, D Tang, C Vallim, T Wimberger, J
Source	PMC
abstract	HDLs are nanoparticles with more than 80 associated proteins, phospholipids, cholesterol, and cholesteryl esters. The potential inverse relation of HDL to coronary artery disease (CAD) and the effects of HDL on myriad other inflammatory conditions warrant a better understanding of the genetic basis of the HDL proteome. We conducted a comprehensive genetic analysis of the regulation of the proteome of HDL isolated from a panel of 100 diverse inbred strains of mice (the hybrid mouse diversity panel) and examined protein composition and efflux capacity to identify novel factors that affect the HDL proteome. Genetic analysis revealed widely varied HDL protein levels across the strains. Some of this variation was explained by local cis-acting regulation, termed cis-protein quantitative trait loci (QTLs). Variations in apoA-II and apoC-3 affected the abundance of multiple HDL proteins, indicating a coordinated regulation. We identified modules of covarying proteins and defined a protein-protein interaction network that describes the protein composition of the naturally occurring subspecies of HDL in mice. Sterol efflux capacity varied up to 3-fold across the strains, and HDL proteins displayed distinct correlation patterns with macrophage and ABCA1-specific cholesterol efflux capacity and cholesterol exchange, suggesting that subspecies of HDL participate in discrete functions. The baseline and stimulated sterol efflux capacity phenotypes were associated with distinct QTLs with smaller effect size, suggesting a multigenetic regulation. Our results highlight the complexity of HDL particles by revealing the high degree of heterogeneity and intercorrelation, some of which is associated with functional variation, and support the concept that HDL-cholesterol alone is not an accurate measure of HDL’s properties, such as protection against CAD.
has issue date	2019-01-08(xsd:dateTime)
bibo:doi	10.1194/jlr.m090555
bibo:pmid	30622162
has license	cc-by
sha1sum (hex)	e5d7b78cf1acf78071a1b54e6f4fe6dd68ac9430
schema:url	https://doi.org/10.1194/jlr.m090555
resource representing a document's title	Genetic control of the mouse HDL proteome defines HDL traits, function, and heterogeneity
has PubMed Central identifier	PMC6399512
has PubMed identifier	30622162
schema:publication	J Lipid Res
resource representing a document's body	covid:e5d7b78cf1acf78071a1b54e6f4fe6dd68ac9430#body_text
is schema:about of	named entity 'HIGH' named entity '27S' named entity 'VARIATION' named entity 'HETEROGENEITY' named entity 'DEGREE' named entity 'CHOLESTEROL' named entity 'PROPERTIES' named entity 'MEASURE' named entity 'ASSOCIATED WITH' named entity 'PROTECTION' named entity 'SUPPORT' named entity 'HDL' named entity 'ACCURATE' named entity 'FUNCTIONAL' named entity 'CONCEPT' named entity 'HDL' named entity 'heterogeneity' named entity 'genetic analysis' named entity 'antigen' named entity 'Apoa2' named entity 'APOD' named entity 'Insulin-like growth factor binding protein' named entity 'HDL' named entity 'cis' named entity 'insulin sensitivity' named entity 'Apoh' named entity 'protein content' named entity 'HDL' named entity 'AxB' named entity 'LCAT' named entity 'insulin' named entity 'protein' named entity 'ammonium bicarbonate' named entity 'HDL' named entity 'ABCA1' named entity 'sucrose' named entity 'ABCA1' named entity 'regulation of gene expression' named entity 'Apoc1' named entity 'HDL' named entity 'macrophage' named entity 'heritability' named entity 'APOC3' named entity 'HDL' named entity 'inflammatory conditions' named entity 'recombinant' named entity 'adiposity' named entity 'APOC3' named entity 'KKHI' named entity 'protein-protein interactions' named entity 'cholesterol' named entity 'HDL-C' named entity 'Lipid metabolism' named entity 'locus' named entity 'acid hydrolysis' named entity 'phenotypes' named entity 'proteome' named entity 'lipoprotein' named entity 'cell types' named entity 'HDL' named entity 'sterol' named entity 'heritability' named entity 'gene' named entity 'heritability' named entity 'GWAS' named entity 'CAD' named entity 'cholesteryl esters' named entity 'hierarchical clustering' named entity 'HDLs' named entity 'linkage disequilibrium' named entity 'gene' named entity 'APOC3' named entity 'HDL'

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