Aspirin Attenuates Angiotensin II ‐induced Cardiomyocyte Hypertrophy by Inhibiting the Ca2+/Calcineurin‐ NFAT Signaling Pathway

INTRODUCTION: In this study, we examined whether aspirin could inhibit cardiac hypertrophy. METHODS: We utilized cultured neonatal mouse cardiomyocytes and mice for the study and subjected to cardiomyocyte immunochemistry, qRT-PCR, and immunoblotting analysis. The cardiac function was measured using M-mode echocardiography. RESULTS: Ten μM aspirin significantly inhibited Ang II-induced increase in cardiomyocyte size, the mRNA, and protein levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC) (P < 0.05). Meantime, consistent with the result in vitro, the increase in HW/BW ratio, the mRNA, and protein levels of ANP, BNP, and β-MHC could be reduced by aspirin in vivo (P < 0.05). Analysis of cardiac function revealed that mouse hearts treated with Ang II displayed thickening of the ventricular walls, left ventricular end-diastolic dimensions, and left ventricular end-systolic dimensions were significantly decreased (P < 0.05), whereas interventricular septal thickness at end-diastole, interventricular septal thickness at end-systole, posterior wall thickness in diastole, and posterior wall thickness in systole were markedly increased (P < 0.05), which could be reversed by aspirin (P < 0.05). Moreover, aspirin blunted the increase inCa(2+) and inhibited the calcineurin activity and NFAT dephosphorylation caused by Ang II (P < 0.05). CONCLUSIONS: Aspirin inhibited cardiac hypertrophy in vitro and in vivo through inhibition of the Ca(2+)/calcineurin-NFAT signaling pathway. Therefore, these findings suggested that aspirin might become a therapeutic option to reduce cardiac hypertrophy.