Key result
Overexpressing miR-29a attenuates AngII-induced LV remodeling in mice by inhibiting collagen deposition and TGF-β.
Why the study?
Although plasma miR-29a was associated with LV remodeling in hypertensive patients, the causal relationship and regulatory mechanism remained unknown.
Does overexpression of miR-29a attenuate angiotensin-II induced left ventricular remodeling in mice?
Does overexpression of miR-29a attenuate angiotensin-II induced left ventricular remodeling in mice?
Overexpression of miR-29a attenuates angiotensin-II induced left ventricular remodeling by inhibiting collagen deposition and the TGF-β/SMAD2/3 pathway in a mouse model.
Supports miR-29a as antifibrotic target in remodeling; hypothesis-generating in mice and requires human validation.
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 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.
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Zhang et al. (2020) studied Left ventricular remodeling. miR-29a overexpression vs. miR-29a knockdown / control was evaluated on Left ventricular remodeling (collagen deposition, TGF-β, and phosphorylated SMAD2/3 expression). Overexpression of miR-29a attenuated AngII-induced left ventricular remodeling in mice by inhibiting collagen deposition, TGF-β, and phosphorylated SMAD2/3 expression.
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