Deficiency for MicroRNA-582 does not impact dilated cardiomyopathy or heart failure induced by pressure overload in vivo

MicroRNAs (miRNAs) are critical post-transcriptional regulators of gene expression and have been extensively implicated in cardiovascular development, homeostasis, and disease. Among them, microRNA-582 (miR-582) has been associated with several non-cardiac pathologies, yet its role in the heart remains poorly characterized despite significant cardiac expression. In this study, we investigated the functional significance of miR-582 in cardiac pathophysiology through both gain- and loss-of-function approaches. We observed differential expression of miR-582 in murine models of cardiomyopathy, prompting further mechanistic evaluation. Thus, we generated transgenic mice with cardiac-specific overexpression of miR-582 (TG-582) as well as miR-582 knockout (582-KO) mice. Neither model exhibited an obvious cardiac phenotype under basal conditions. Following pressure overload via transverse aortic constriction (TAC), both TG-582 and 582-KO mice developed hypertrophy and functional adaptations comparable to wildtype controls. Additionally, crossbreeding these models with Calsarcin-1-knockout (CS1-KO) mice, a model of dilated cardiomyopathy, did not modify the pathological phenotype. These results indicate that miR-582 does not play a determinative role in pressure overload-induced cardiac hypertrophy or in the progression of dilated cardiomyopathy. Our findings highlight the importance of rigorously controlled <i>in vivo</i> studies to accurately define the cardiac miRNA landscape and to guide future therapeutic strategies.