The Role of MiR‐21 in Right Ventricular Remodeling Secondary to Pulmonary Arterial Pressure Overload

Abstract

Pulmonary arterial hypertension (PAH) prognosis is related to the degree of right ventricular (RV) dysfunction. While the effects of pulmonary pressure overload on RV remodeling are largely unknown, microRNA‐21 (miR‐21) has been identified as a factor involved in PAH vasculature remodeling and cellular hypertrophy. The goal of this study is to characterize regional structural and functional change in RV after PAH and identify the role of miR‐21. Pulmonary arterial constriction (PAC) induced PAH in 5‐month‐old adult male sheep. Longitudinal echocardiography was used to monitor functional and structural changes. After four weeks, hearts were harvested for histological and molecular examination. Isolated neonatal rat ventricular myocytes (NRVM) were used to define the role of miR‐21 in cardiomyocytes (CM). Elevated PA pressure led to increased RV weight and thickness in PAC sheep. Decreased systolic function was most profound in the RV basal region. Following changes in regional function, miR‐21 was also differentially upregulated in the basal region as determined by RT‐PCR. Interestingly, NRVM treated with a miR‐21 mimic increased mitosis but not cytokinesis compared to controls. Congruently, RV basal CM isolated from PAC animals revealed increased elongated multinuclear cells, supporting the notion of RV pressure overload‐induced hypertrophy. We conclude that PAC led to regional alterations and contributes to adverse global functional changes. The differential upregulation of miR‐21 in basal and altered RV CM remodeling may indicate PAC‐induced regional and global structural and functional RV remodeling.