Fig. 4

The role of hypoxia and metabolic transition during cardiac development. Significant changes in metabolic pathways accompany the maturation of cardiac development. During embryonic cardiac development, glucose and lactate serve as the primary sources of ATP. Hypoxic conditions activate HIF-1α during embryonic development, coupled with mitochondrial immaturity, which promotes a reliance on glycolysis for ATP production in the fetal heart, leading to increased lactate production. As cardiac development progresses, there is a simultaneous decrease in glycolysis and an increase in fatty acid β-oxidation during myocardial maturation. After birth, cardiac metabolism primarily relies on fatty acid oxidation, facilitated by an oxygen-rich environment. In this environment, the HIF-1α subunit is hydroxylated and targeted for degradation by VHL, thereby inhibiting its promotion of glycolysis. α-KG α-ketoglutarate, ATP adenosine triphosphate, CoA coenzyme A, HIF-1α hypoxia-inducible factor 1-alpha, OH hydroxide, O₂ oxygen, TCA tricarboxylic acid, VHL von Hippel Lindau. This figure was created using Adobe Illustrator