MicroRNA-29a attenuates angiotensin-II induced-left ventricular remodeling by inhibiting collagen, TGF-β and SMAD2/3 expression

Background Left ventricular (LV) remodeling is the most common target organ damage in hypertension. Previously, our study found that plasma microRNA-29a (miR-29a) level was associated with the LV remodeling in hypertensive patients. However, the causal relationship between miR-29a and LV remodeling remains unknown. Thus, the aim of this study was to investigate the regulation mechanism of miR-29a in LV remodeling. Methods & Results Overexpression and knockdown miR-29a mice were generated by tail-intravenous injection of miR-29a-mimic and inhibitor lentivirus for one week respectively. Then the mice were subjected to angiotensin-II (AngII) induced LV remodeling by subcutaneous AngII capsule osmotic pumping into AngII for four weeks. AngII-induced LV remodeling mice as the model group (n = 9). Age-matched male SPF C57/BL6J mice (6–8 weeks old) were treated with the pumping of saline as a vehicle (n = 6). In vivo, overexpression miR-29a ameliorated AngII-induced LV remodeling, while knockdown miR-29a deteriorated LV remodeling. Simultaneously, we observed that overexpression miR-29a mice inhibited but knockdown miR-29a mice increased cardiac cross-sectional area, indicating that miR-29a has an antagonistic effect on cardiac hypertrophy. Further studies found that overexpression miR-29a inhibited the content of the LV collagen including collagen I and III. Moreover, the expression of transforming growth factor-β (TGF-β) and phosphorylated SMAD2/3 decreased with the down-regulation of collagen I and III in overexpression miR-29a mice. Conclusions Our finding indicates that overexpression miR-29a attenuates LV remodeling by inhibiting collagen deposition, TGF-β, and phosphorylated SMAD2/3 expression. Thus, intervention miR-29a may be a therapeutic target for attenuating LV remodeling.