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.
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May 08 2015
SRY gene transferred by extracellular vesicles accelerates atherosclerosis by promotion of leucocyte adherence to endothelial cells
Jin Cai;
Jin Cai
1
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Weiwei Guan;
Weiwei Guan
1
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Xiaorong Tan;
Xiaorong Tan
1
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Caiyu Chen;
Caiyu Chen
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Liangpeng Li;
Liangpeng Li
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Na Wang;
Na Wang
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Xue Zou;
Xue Zou
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Faying Zhou;
Faying Zhou
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Jialiang Wang;
Jialiang Wang
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Fang Pei;
Fang Pei
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Xinjian Chen;
Xinjian Chen
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Hao Luo;
Hao Luo
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Xinquan Wang;
Xinquan Wang
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Duofen He;
Duofen He
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
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Lin Zhou;
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
Correspondence: Dr Chunyu Zeng (email [email protected]) or Dr Lin Zhou (email [email protected]).
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Pedro A. Jose;
Pedro A. Jose
†Division of Nephrology, Department of Medicine and Physiology, University of Maryland, School of Medicine, Baltimore, MD 21201, U.S.A.
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Chunyu Zeng
*Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
Correspondence: Dr Chunyu Zeng (email [email protected]) or Dr Lin Zhou (email [email protected]).
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Publisher: Portland Press Ltd
Received:
December 16 2014
Revision Received:
March 13 2015
Accepted:
March 18 2015
Accepted Manuscript online:
March 18 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2015 Biochemical Society
2015
Clin Sci (Lond) (2015) 129 (3): 259–269.
Article history
Received:
December 16 2014
Revision Received:
March 13 2015
Accepted:
March 18 2015
Accepted Manuscript online:
March 18 2015
Citation
Jin Cai, Weiwei Guan, Xiaorong Tan, Caiyu Chen, Liangpeng Li, Na Wang, Xue Zou, Faying Zhou, Jialiang Wang, Fang Pei, Xinjian Chen, Hao Luo, Xinquan Wang, Duofen He, Lin Zhou, Pedro A. Jose, Chunyu Zeng; SRY gene transferred by extracellular vesicles accelerates atherosclerosis by promotion of leucocyte adherence to endothelial cells. Clin Sci (Lond) 1 August 2015; 129 (3): 259–269. doi: https://doi.org/10.1042/CS20140826
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