PGAM1 deficiency ameliorates myocardial infarction remodeling by targeting TGF-β via the suppression of inflammation, apoptosis and fibrosis.

Myocardial ischemia-reperfusion (MIR) represents critical challenge for the treatment of acute myocardial infarction diseases. Presently, identifying the molecular basis revealing MIR progression is scientifically essential and may provide effective therapeutic strategies. Phosphoglycerate mutase 1 (PGAM1) is a key aerobic glycolysis enzyme, and exhibits critical role in mediating several biological events, such as energy production and inflammation. However, whether PGAM1 can affect MIR is unknown. Here we showed that PGAM1 levels were increased in murine ischemic hearts. Mice with cardiac knockout of PGAM1 were resistant to MIR-induced heart injury, evidenced by the markedly reduced infarct volume, improved cardiac function and histological alterations in cardiac sections. In addition, inflammatory response, apoptosis and fibrosis in hearts of mice with MIR operation were significantly alleviated by the cardiac deletion of PGAM1. Mechanistically, the activation of nuclear transcription factor κB (NF-κB), p38, c-Jun NH2-terminal kinase (JNK) and transforming growth factor β (TGF-β) signaling pathways were effectively abrogated in MI-operated mice with specific knockout of PGAM1 in hearts. The potential of PGAM1 suppression to inhibit inflammatory response, apoptosis and fibrosis were verified in the isolated cardiomyocytes and fibroblasts treated with oxygen-glucose deprivation reperfusion (OGDR) and TGF-β, respectively. Importantly, PGAM1 directly interacted with TGF-β to subsequently mediate inflammation, apoptosis and collagen accumulation, thereby achieving its anti-MIR action. Collectively, these findings demonstrated that PGAM1 was a positive regulator of myocardial infarction remodeling due to its promotional modulation of TGF-β signaling, indicating that PGAM1 may be a promising therapeutic target for MIR treatment.