Fig. 9: A proposed model of the mechanism underlying myocardial energy metabolism remodeling and HF induced by HP.
From: IRF1-mediated downregulation of PGC1α contributes to cardiorenal syndrome type 4
High phosphate (HP) enters cardiomyocytes via Pit1 and Pit2, and induces IRF1 expression through acetylating histone H3K9 in the IRF1 promoter region, during which histone acetyltransferases (HAT) are involved. HP-induced IRF1 inhibits PGC1α expression via directly binding to its promoter region (−632 to −612). PGC1α downregulation contributes to HP-induced mitochondrial dysfunction and myocardial energy metabolism remodeling. Restoration of PGC1α expression or knockdown of IRF1 protects against CKD-associated myocardial energy metabolism remodeling and HF.
