Senescente P16+ cellen verergeren hartremodellering na ischemie via cytotoxische lymfocyten

BACKGROUND:Ischemic heart disease remains a leading cause of mortality worldwide, with adverse remodeling after myocardial infarction driven by inflammation and cardiomyocyte loss. Although cytotoxic lymphocytes exacerbate myocardial injury and P16 marks cellular senescence in diseased hearts, the cell type–specific functions of P16+populations remain unclear.METHODS:Usingp16-CreER;R26-tdTreporter mice, we mapped P16+cell heterogeneity after myocardial infarction. Senolytic effects were assessed with combined dasatinib and quercetin treatment. Transcriptomic profiling (bulk and single-cell RNA sequencing) of sorted P16+cells identified secreted factors, validated through in silico predictions and quantitative polymerase chain reaction. Intercellular communication was analyzed using CellChat. Functional relevance was tested through CCL8 (cytokine [C-C motif] ligand 8) neutralization,Ccl8deletion in P16+cells, lymphocyte depletion, and intersectional genetic ablation of P16+fibroblasts o