title: Secreted miR-27a Induced by Cyclic Stretch Modulates the Proliferation of Endothelial Cells in Hypertension via GRK6.
abstract: Abnormal proliferation of endothelial cells (ECs) is important in vascular remodeling during hypertension, but the mechanisms are still unclear. In hypertensive rats caused by abdominal aortic coarctation, the expression of G-protein-coupled receptor kinase 6 (GRK6) in ECs at common carotid artery was repressed in vivo, and EC proliferation was increased. 15% cyclic stretch in vitro, which mimics the pathologically increased stretch in hypertension, repressed EC GRK6 expression via paracrine control by vascular smooth muscle cells (VSMCs). Furthermore, VSMC-derived microparticles (VSMC-MPs) were detected in the conditioned medium from VSMCs and in artery. VSMC-MPs from cells exposed to 15% cyclic stretch decreased GRK6 expression and increased EC proliferation. miR-27a was detected in VSMC-MPs and was upregulated by 15% cyclic stretch. miR-27a was transferred from VSMCs to ECs via VSMC-MPs and directly targeted on GRK6. Finally, a multi-point injection of antagomiR-27a around carotid artery decreased miR-27a expression in vivo, induced GRK6 expression, and reversed the abnormal EC proliferation. Pathologically elevated cyclic stretch increased the secretion of miR-27a, which was transferred from VSMCs to ECs via the VSMC-MPs, subsequently targeted GRK6, and induced EC proliferation. Locally decreasing miR-27a could be a novel therapeutic approach to attenuate the abnormal EC proliferation in hypertension.
authors.affiliation: Institute of Mechanobiology &Medical Engineering, School of Life Sciences &Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Mechanobiology &Medical Engineering, School of Life Sciences &Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Han
authors.initials: H
authors.lastname: Bao
authors.affiliation: Institute of Mechanobiology &Medical Engineering, School of Life Sciences &Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Kai-Xuan
authors.initials: KX
authors.lastname: Wang
authors.affiliation: Institute of Mechanobiology &Medical Engineering, School of Life Sciences &Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Mechanobiology &Medical Engineering, School of Life Sciences &Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Yao
authors.affiliation: Institute of Mechanobiology &Medical Engineering, School of Life Sciences &Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiao-Hu
authors.initials: XH
authors.lastname: Chen
authors.affiliation: Institute of Mechanobiology &Medical Engineering, School of Life Sciences &Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.affiliation: Institute of Mechanobiology &Medical Engineering, School of Life Sciences &Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ying-Xin
authors.initials: YX
authors.lastname: Qi
authors.affiliation: Institute of Mechanobiology &Medical Engineering, School of Life Sciences &Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zong-Lai
authors.initials: ZL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D054768:G-Protein-Coupled Receptor Kinases / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D019899:Paracrine Communication; D010812:Physical Stimulation; D017207:Rats, Sprague-Dawley
chemical_list: C000594049:MIRN27 microRNA, rat; D035683:MicroRNAs; D054768:G-Protein-Coupled Receptor Kinases; C089176:G-protein-coupled receptor kinase 6