Cardiac fibroblasts secrete miRNA-enriched exosomes that mediate cardiomyocyte hypertrophy. This study reveals that cardiac fibroblasts release exosomes containing miRNA passenger strands, particularly miR-21*, which act as paracrine signaling molecules to induce cardiomyocyte hypertrophy. miR-21* is enriched in fibroblast-derived exosomes and is transported to cardiomyocytes, where it targets SORBS2 and PDLIM5, leading to hypertrophy. miR-21* is regulated by NSMASE2 and its levels increase under pathological conditions such as Ang II-induced hypertrophy. Inhibition of miR-21* in mice reduces cardiac hypertrophy, suggesting its potential as a therapeutic target. The findings highlight the role of miR-21* in fibroblast-cardiomyocyte communication and its involvement in cardiac remodeling and failure. The study demonstrates that miR-21* is a key paracrine signaling mediator in cardiac hypertrophy, with implications for therapeutic interventions.Cardiac fibroblasts secrete miRNA-enriched exosomes that mediate cardiomyocyte hypertrophy. This study reveals that cardiac fibroblasts release exosomes containing miRNA passenger strands, particularly miR-21*, which act as paracrine signaling molecules to induce cardiomyocyte hypertrophy. miR-21* is enriched in fibroblast-derived exosomes and is transported to cardiomyocytes, where it targets SORBS2 and PDLIM5, leading to hypertrophy. miR-21* is regulated by NSMASE2 and its levels increase under pathological conditions such as Ang II-induced hypertrophy. Inhibition of miR-21* in mice reduces cardiac hypertrophy, suggesting its potential as a therapeutic target. The findings highlight the role of miR-21* in fibroblast-cardiomyocyte communication and its involvement in cardiac remodeling and failure. The study demonstrates that miR-21* is a key paracrine signaling mediator in cardiac hypertrophy, with implications for therapeutic interventions.