This study investigates the role of cardiac fibroblasts in mediating cardiomyocyte hypertrophy through the secretion of microRNA-enriched exosomes. Cardiac fibroblasts were found to produce and release exosomes that are enriched with "star" miRNAs, specifically miR-21*. Confocal imaging and coculture assays revealed that miR-21* is transported from fibroblasts to cardiomyocytes, where it induces hypertrophy by targeting and regulating the expression of SORBS2 and PDLLIM5. In vivo experiments in mice with Ang II-induced cardiac hypertrophy showed that pharmacological inhibition of miR-21* attenuated the hypertrophic phenotype. These findings highlight a novel paracrine signaling mechanism involving cardiac fibroblasts and cardiomyocytes, with miR-21* identified as a potential therapeutic target for cardiac failure.This study investigates the role of cardiac fibroblasts in mediating cardiomyocyte hypertrophy through the secretion of microRNA-enriched exosomes. Cardiac fibroblasts were found to produce and release exosomes that are enriched with "star" miRNAs, specifically miR-21*. Confocal imaging and coculture assays revealed that miR-21* is transported from fibroblasts to cardiomyocytes, where it induces hypertrophy by targeting and regulating the expression of SORBS2 and PDLLIM5. In vivo experiments in mice with Ang II-induced cardiac hypertrophy showed that pharmacological inhibition of miR-21* attenuated the hypertrophic phenotype. These findings highlight a novel paracrine signaling mechanism involving cardiac fibroblasts and cardiomyocytes, with miR-21* identified as a potential therapeutic target for cardiac failure.