title: SRY gene transferred by extracellular vesicles accelerates atherosclerosis by promotion of leucocyte adherence to endothelial cells.
abstract: We set out to investigate whether and how SRY (sex-determining region, Y) DNAs in plasma EVs (extracellular vesicles) is involved in the pathogenesis of atherosclerosis. PCR and gene sequencing found the SRY gene fragment in plasma EVs from male, but not female, patients; EVs from male patients with CAD (coronary artery disease) had a higher SRY GCN (gene copy number) than healthy subjects. Additional studies found that leucocytes, the major source of plasma EVs, had higher SRY GCN and mRNA and protein expression in male CAD patients than controls. After incubation with EVs from SRY-transfected HEK (human embryonic kidney)-293 cells, monocytes (THP-1) and HUVECs (human umbilical vein endothelial cells), which do not endogenously express SRY protein, were found to express newly synthesized SRY protein. This resulted in an increase in the adherence factors CD11-a in THP-1 cells and ICAM-1 (intercellular adhesion molecule 1) in HUVECs. EMSA showed that SRY protein increased the promoter activity of CD11-a in THP-1 cells and ICAM-1 in HUVECs. There was an increase in THP-1 cells adherent to HUVECs after incubation with SRY-EVs. SRY DNAs transferred from EVs have pathophysiological significance in vivo; injection of SRY EVs into ApoE-/- (apolipoprotein-knockout) mice accelerated atherosclerosis. The SRY gene in plasma EVs transferred to vascular endothelial cells may play an important role in the pathogenesis of atherosclerosis; this mechanism provides a new approach to the understanding of inheritable CAD in men.
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cai
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Guan
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Tan
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Caiyu
authors.initials: C
authors.lastname: Chen
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Liangpeng
authors.initials: L
authors.lastname: Li
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zou
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Faying
authors.initials: F
authors.lastname: Zhou
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Pei
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Chen
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Luo
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Wang
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Duofen
authors.initials: D
authors.lastname: He
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: †Division of Nephrology, Department of Medicine and Physiology, University of Maryland, School of Medicine, Baltimore, MD 21201, U.S.A.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.affiliation: *Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D051876:Sex-Determining Region Y Protein / Q000235:genetics / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; C497746:Sry protein, mouse; D019010:Vascular Cell Adhesion Molecule-1