In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-01-20)
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.
Type of Medium:
Online Resource
ISSN:
2045-2322
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2017
detail.hit.zdb_id:
2615211-3
