P16^INK4a promotes myocardial ischemia-reperfusion injury by regulating bile acid transport via Slco1a4.

ABSTRACT: Myocardial ischemia-reperfusion (I/R) injury remains a significant challenge in cardiovascular medicine, with its molecular mechanisms still not fully understood. Screening the GEO and Comparative Toxicogenomics Database as well as spatial multi-omics data, we identify Cdkn2a, encoding p16^INK4a, as a determinant in I/R injury. Cdkn2a expression is elevated in the myocardium of ischemic cardiomyopathy patients and p16^INK4a protein is enriched in cardiomyocytes within ischemic zones of myocardial infarction tissues. We find that p16^INK4a is consistently upregulated in both in vivo and in vitro I/R models, promoting apoptosis in neonatal rat cardiomyocytes (NRCMs) and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) exposed to oxygen-glucose depriva

SUBMITTER: Yang T 

PROVIDER: S-EPMC12936097 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature