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However, their roles in cardiomyocyte proliferation and hypertrophy remain incompletely understood. In this study, we investigated the effects of PPAR\u2010\u03b1 and PPAR\u2010\u03b3 modulation on neonatal rat cardiomyocytes (NRCMs) using pharmacological agonists (WY\u201014643 for PPAR\u2010\u03b1 and pioglitazone for PPAR\u2010\u03b3) and inhibitors (MK\u2010886 for PPAR\u2010\u03b1 and GW9662 for PPAR\u2010\u03b3), as well as siRNA\u2010mediated knockdown approaches. Cardiomyocyte proliferation and hypertrophy were assessed by immunofluorescence, cell size measurements, and proliferation assays. Our findings demonstrate that PPAR\u2010\u03b1 activation significantly promotes cardiomyocyte proliferation and reduces hypertrophy, whereas PPAR\u2010\u03b1 inhibition induces hypertrophic changes and suppresses proliferation. Similarly, PPAR\u2010\u03b3 activation enhances both proliferation and hypertrophy of cardiomyocytes, suggesting its involvement in physiological hypertrophy and a potential protective role in pathological remodeling. In contrast, pharmacological activation or genetic inhibition of PPAR\u2010\u03b4 showed no significant effects on cardiomyocyte proliferation or hypertrophy, highlighting its distinct role in metabolic homeostasis rather than structural remodeling. PPAR\u2010\u03b1 and PPAR\u2010\u03b3 play distinct but complementary roles in regulating cardiomyocyte proliferation and hypertrophy. These results suggest that targeting PPAR\u2010\u03b1 and PPAR\u2010\u03b3 may represent promising therapeutic strategies for cardiac hypertrophy and heart failure. Further in\u00a0vivo studies are warranted to clarify their molecular mechanisms and potential clinical applications.<\/jats:p>","DOI":"10.1002\/iub.70035","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T11:50:33Z","timestamp":1750333833000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Modulation of <scp>PPAR<\/scp>\u2010\u03b1 and <scp>PPAR<\/scp>\u2010\u03b3 Influences Cardiomyocyte Growth and Cardiac Remodeling"],"prefix":"10.1002","volume":"77","author":[{"given":"Qinkao","family":"Xuan","sequence":"first","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Infectious Diseases Hospital of Soochow University  Suzhou Jiangsu 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