title: ABCG1 deficiency promotes endothelial apoptosis by endoplasmic reticulum stress-dependent pathway.
abstract: The present study was focused on whether ABCG1 deficiency was involved in endothelial apoptosis and its possible mechanism. Human umbilical artery endothelial cells were transfected with ABCG1 siRNA and/or ABCG1 expression plasmid. We observed that silencing of endothelial ABCG1 reduced cholesterol efflux to HDL and increased intracellular lipid content. Moreover, reduction of ABCG1 promoted endothelial apoptosis and expression of endoplasmic reticulum (ER) stress-related molecules GRP78 and CHOP. In contrast, transfection of ABCG1 overexpression plasmid reversed endothelial apoptosis and intracellular lipid accumulation as well as decreased expression of GRP78 and CHOP in ABCG1-deficient endothelial cells. Furthermore, endothelial apoptosis and ER stress-related molecules were induced by repletion of endothelial cells with cholesterol-loaded cyclodextrin, otherwise endothelial apoptotic response and expression of GRP78 and CHOP were suppressed by depletion of cellular cholesterol in ABCG1-deficient endothelial cells. The present results suggest that reduction of ABCG1 induces endothelial apoptosis, which seems associated with intracellular free cholesterol accumulation and subsequent ER stress.
authors.affiliation: Department of Cardiovascular Medicine, Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, 157 West Five Road, Xi'an, 710004, Shaanxi, China, xjh1224@163.com.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Xue
authors.forename: Jin
authors.initials: J
authors.lastname: Wei
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.forename: Canzhan
authors.initials: C
authors.lastname: Zhu
authors.forename: Yongqin
authors.initials: Y
authors.lastname: Li
authors.forename: Anqi
authors.initials: A
authors.lastname: Song
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000172:deficiency*; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D042783:Endothelial Cells / Q000473:pathology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D051742:Transcription Factor CHOP; D002784:Cholesterol
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