Hypoxia promotes mitochondrial biogenesis in myocardium of broiler with pulmonary hypertension syndrome through AMPK/PGC-1 alpha pathway.

Abstract

Hypoxia is a leading cause of myocardial damage and pulmonary hypertension syndrome (PHS) in broiler. Congenital or acquired myocardial dysfunction is associated with abnormal expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and its target gene. Here, we investigate the relationship between PGC-1α expression and mitochondrial biogenesis in cardiomyocytes of PHS broiler. For in vivo study, PHS was induced by intravenously injection of CM-32 cellulose through wing vien. For in vitro study, a hypoxia chamber was used, and cardiomyocytes from broiler were cultured with or without hypoxia treatment. The result showed that PGC-1α expression in myocardia of PHS broiler was significantly increased compared with birds in control group. Transmission electron microscopy revealed an increased quantity of mitochondria and ultrastructural abnormalities in myocardial of PHS broiler. Histopathological examinations indicated that the myocardial tissues of PHS broilers showed varying degrees of degenerative remodel compared with controls. In vitro studies showed that hypoxia induced an increase in ROS production, promoted PGC-1α expression, stimulated mitochondrial biosynthesis, and increased ATP content in cardiomyocytes. Further studies suggest that hypoxia-induced PGC-1α expression is regulated through the AMPK signaling pathway. In conclusion, our data suggest that hypoxia stimulates PGC-1α expression and mitochondrial biosynthesis in cardiomyocytes. This process may provide a potential adaptive mechanism for cardiomyocytes to increase ATP production to attenuate hypoxic damage to the heart in the pathological process of PHS.