title: Endothelial-specific expression of mitochondrial thioredoxin improves endothelial cell function and reduces atherosclerotic lesions.
abstract: The function of the mitochondrial antioxidant system thioredoxin (Trx2) in vasculature is not understood. By using endothelial cell (EC)-specific transgenesis of the mitochondrial form of the thioredoxin gene in mice (Trx2 TG), we show the critical roles of Trx2 in regulating endothelium functions. Trx2 TG mice have increased total antioxidants, reduced oxidative stress, and increased nitric oxide (NO) levels in serum compared with their control littermates. Consistently, aortas from Trx2 TG mice show reduced vasoconstriction and enhanced vasodilation. By using ECs isolated from Trx2 TG mice, we further show that Trx2 increases the capacities of ECs in scavenging reactive oxygen species generated from mitochondria, resulting in increases in NO bioavailability in ECs. More importantly, Trx2 improves EC function and reduces atherosclerotic lesions in the apolipoprotein E-deficient mouse model. Our data provide the first evidence that Trx2 plays a critical role in preserving vascular EC function and prevention of atherosclerosis development, in part by reducing oxidative stress and increasing NO bioavailability.
authors.affiliation: Interdepartmental Program in Vascular Biology and Transplantation, Department of Pathology, Yale University School of Medicine, BCMM 454, 295 Congress Ave., New Haven, CT 06510, USA.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: He
authors.forename: Shengchuan
authors.initials: S
authors.lastname: Dai
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Pascal
authors.initials: P
authors.lastname: Bernatchez
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Giordano
authors.forename: Gerald
authors.initials: G
authors.lastname: Shadel
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
authors.forename: Wang
authors.initials: W
authors.lastname: Min
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D014664:Vasodilation
chemical_list: D001057:Apolipoproteins E; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D013879:Thioredoxins