The antagonistic effects and mechanisms of microRNA-26a action in hypertensive vascular remodelling

Hypertensive vascular remodelling is responsible for end-organ damage and is the result of increased extracellular matrix accumulation and excessive vascular smooth muscle cell (VSMC) proliferation. MicroRNA-26a (miR-26a), a non-coding small RNA, is involved in several cardiovascular diseases. We aimed to validate the effect and mechanisms of miR-26a in hypertensive vascular remodelling. Experimental approach: Male spontaneously hypertensive rats (SHRs) were injected intravenously with recombinant adeno-associated virus-miR-26a. Samples of thoracic aorta were examined histologically with H&E staining. In vitro, angiotensin II (AngII)-induced VSMCs cultured from thoracic aortae of female Sprague-Dawley rats, were transfected with miR-26a mimic or inhibitor. Western blots, qRT-PCR and immunohistological

Hypertensive vascular remodelling is responsible for end-organ damage and is the result of increased extracellular matrix accumulation and excessive vascular smooth muscle cell (VSMC) proliferation. MicroRNA-26a (miR-26a), a non-coding small RNA, is involved in several cardiovascular diseases. We aimed to validate the effect and mechanisms of miR-26a in hypertensive vascular remodelling. Experimental approach: Male spontaneously hypertensive rats (SHRs) were injected intravenously with recombinant adeno-associated virus-miR-26a. Samples of thoracic aorta were examined histologically with H&E staining. In vitro, angiotensin II (AngII)-induced VSMCs cultured from thoracic aortae of female Sprague-Dawley rats, were transfected with miR-26a mimic or inhibitor. Western blots, qRT-PCR and immunohistological

Levels of miR-26a were lower in the thoracic aorta and plasma of SHRs than in WKY rats. Overexpression of miR-26a inhibited extracellular matrix deposition by targeting connective tissue growth factor (CTGF) and decreased VSMC proliferation by regulating the enhancer of zeste homologue 2 (EZH2)/p21 pathway both in vitro and in vivo. AngII-mediated Smad3 activation suppressed miR-26a expression, which in turn promoted Smad3 activation via targeted regulation of Smad4, leading to further down-regulation of miR-26a.