Anti-hypertrophy effect of atorvastatin on myocardium depends on AMPK activation-induced miR-143-3p suppression via Foxo1.

Left ventricular hypertrophy (LVH) is a pathological characteristic shared by distinct heart disorders. Atorvastatin is employed as a lipid lowering agent and its heart protection effect has been recently reported as well. Thus, the current study attempted to validate the anti-hypertrophy effect of atorvastatin as well as the associated mechanism. Hypertrophic feature was induced in rats using transverse aortic constriction (TAC) method and in cardiomyocytes using angiotensin II (Ang II). Then the animals and cells were treated with atorvastatin and the effect on cardiac weight and structure as well as cell viability, surface area, and apoptosis was assessed. The mechanism associated with the anti-hypertrophy effect of atorvastatin was further explored by focusing on the AMPK/Foxo1/miR-143-3p axis. The results showed that the administration of atorvastatin significantly suppressed TAC-induced heart weight increase and attenuated cardiac structure deteriorations in rats. In in vitro assays, atorvastatin increased cell viability, and reduced cell surface area and apoptosis in Ang II-treated H9c2 cells. At molecular level, atorvastatin activated AMPK, which further promoted Foxo1 activation and suppressed miR-143-3p level. The key role of AMPK during atorvastatin treatment was further validated by subjecting Ang II-treated H9c2 cells to co-incubation of atorvastatin and Compound C, which blocked the pro-survival and anti-hypertrophy effect of atorvastatin on H9c2 cells. The findings outlined in the current study confirmed the anti-hypertrophy effect of atorvastatin and provided a preliminary explanation on the mechanism associated with the treatment: the protective effect of atorvastatin on myocardium against hypertrophy depended on miR-143-3p inhibition via AMPK and Foxo1 activation.