Supplementary file 1_PMEPA1 attenuates myocardial ischemia-reperfusion injury via interaction with NEDD4 and involvement of the TGF-β/SMAD pathway.docx

Introduction<p>Myocardial ischemia-reperfusion injury (MIRI) remains a significant challenge in cardiovascular medicine, and its molecular mechanisms are not yet fully elucidated.</p>Methods<p>In the present study, integrated transcriptomic analysis combined with machine learning identified PMEPA1 as a key gene consistently downregulated in both rat models of MIRI and H9c2 cardiomyocytes subjected to ischemia –reperfusion injury.

A series of in vivo and in vitro experiments, including gene overexpression and knockdown, cell viability and proliferation assays, flow cytometry, Western blot, co-immunoprecipitation, and immunofluorescence, were performed to investigate the role and underlying mechanism of PMEPA1 in MIRI.</p>Results<p>Overexpression of PMEPA1 enhanced cardiomyocyte proliferation, reduced apoptosis, and inhibited activation of the TGF-β/SMAD signaling pathway.