Figure 1. A metabolic conversation between cardiac myocytes and fibroblasts disrupts nonmyocyte cell function in post-MI wound healing.

(i) Cardiomyocyte-derived extracellular ATP is metabolized to AMP by cardiac fibroblast ENPP1. (ii) ENPP1-derived AMP is metabolized to adenine within cardiomyocytes and released into the extracellular space. (iii) Cardiomyocyte-derived adenine and other purine nucleosides inhibit pyrimidine synthesis in nonmyocyte cells. (iv) Purine-pyrimidine imbalance in nonmyocyte cells leads to genotoxic stress, cell death, and poor wound-healing outcomes.