MiR-338-5p ameliorates pathological cardiac hypertrophy by targeting CAMKIIδ.

Pathological cardiac hypertrophy (PCH) is characterized by an increase in cardiomyocyte size and thickening of the ventricular walls during the adaptive response to maintain cardiac function, which often progresses to a maladaptive response and, ultimately, to heart failure. Previous studies have demonstrated that miRNAs play roles in the pathogenesis of PCH. In this study, we first found that the regulation of miR-338-5p was aberrant in cardiac tissues of heart failure patients and transverse aortic constriction (TAC)-induced PCH mice. Overexpression of miR-338-5p in the heart using recombinant adeno-associated virus serotype 9 (rAAV9) ameliorated TAC-induced PCH, as indicated by a decreased heart weight/body weight (HW/BW) ratio. Furthermore, miR-338-5p mitigated the TAC-induced damage in heart contraction and relaxation function, as measured by echocardiography and a cardio hemodynamic measurement, respectively. We also identified CAMKIIδ as a direct target of miR-338-5p using bioinformatics tools and the luciferase reporter assay. Finally, we observed that the miR-338-5p-mediated downregulation of CAMKIIδ reversed the cell surface area enlargement induced by the Ang-II treatment in H9c2 cells. Therefore, we highlight a novel molecular mechanism of the miR-338-5p/CAMKIIδ axis that contributes to the pathogenesis of PCH.