부산대학교 도서관

Pathological cardiac hypertrophy (PCH) is characterizedby an increase in cardiomyocyte size and thickeningof the ventricular walls during the adaptive responseto maintain cardiac function, which often progresses to amaladaptive response and, ultimately, to heart failure. Previousstudies have demonstrated that miRNAs play roles inthe pathogenesis of PCH. In this study, we first found thatthe regulation of miR-338-5p was aberrant in cardiac tissuesof heart failure patients and transverse aortic constriction(TAC)-induced PCH mice. Overexpression of miR-338-5p inthe heart using recombinant adeno-associated virus serotype9 (rAAV9) ameliorated TAC-induced PCH, as indicated bya decreased heart weight/body weight (HW/BW) ratio. Furthermore,miR-338-5p mitigated the TAC-induced damagein heart contraction and relaxation function, as measured byechocardiography and a cardio hemodynamic measurement,respectively. We also identified CAMKIIδ as a direct targetof miR-338-5p using bioinformatics tools and the luciferasereporter assay. Finally, we observed that the miR-338-5pmediateddownregulation of CAMKIIδ reversed the cellsurface area enlargement induced by the Ang-II treatmentin H9c2 cells. Therefore, we highlight a novel molecularmechanism of the miR-338-5p/CAMKIIδ axis that contributesto the pathogenesis of PCH.