SRY gene transferred by extracellular vesicles accelerates atherosclerosis by promotion of leucocyte adherence to endothelial cells

Clinical Science
Jin CaiChunyu Zeng

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 Apo...Continue Reading

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Citations

Sep 30, 2016·PloS One·Stefanie FischerClaudia Lange
Oct 25, 2016·Experimental Cell Research·Jin CaiChunyu Zeng
May 13, 2017·Circulation Research·Frank A W CoumansRienk Nieuwland
Oct 31, 2019·Journal of Cardiovascular Translational Research·Mengna PengGelin Xu
May 29, 2018·Journal of Cardiovascular Translational Research·Mengmeng LuShaogui Wan
Feb 1, 2020·Journal of Extracellular Vesicles·Maria S PanagopoulouChristopher D Gregory
May 1, 2020·Frontiers in Cell and Developmental Biology·Hara T GeorgatzakouMarianna H Antonelou
Jul 29, 2020·Cell Death & Disease·Ethan Z Malkin, Scott V Bratman
Jun 20, 2020·DNA and Cell Biology·Xiulin ChangZhibiao Wang
Jul 11, 2018·International Journal of Molecular Sciences·Matilde AliqueRafael Ramírez
Nov 18, 2019·Critical Reviews in Oncology/hematology·Mara FernandesRui Medeiros
Apr 24, 2020·Atherosclerosis·Qiang WangYongjian Yang
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Olga E AndreevaMikhail A Krasil'nikov
Jul 3, 2021·International Journal of Molecular Sciences·Rossana DomenisFrancesco Curcio

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