P16+ Cells Drive Adverse Postischemic Cardiac Remodeling Through CCL8-Mediated Recruitment of Cytotoxic Lymphocytes - PubMed
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- #myocardial infarction
- #P16
- #CCL8
- P16+ cells, including fibroblasts, macrophages, coronary endothelial cells, and cardiomyocytes, are induced after myocardial infarction (MI).
- Dasatinib and quercetin treatment selectively eliminates P16+ macrophages and fibroblasts, improving cardiac function post-MI.
- P16+ fibroblasts and macrophages are the main sources of CCL8, which recruits cytotoxic lymphocytes (CD8+ T cells and NK cells).
- CCL8 blockade or genetic deletion in P16+ cells reduces cytotoxic lymphocyte infiltration, decreases cardiomyocyte apoptosis, and enhances repair.
- Ablation of P16+ fibroblasts (but not macrophages) reduces fibrosis and improves cardiac function, while CD8+ T cell depletion attenuates adverse remodeling.
- Targeting P16+ fibroblasts or blocking CCL8 presents a promising therapeutic strategy for ischemic heart disease.