This review strongly believes that the Reperfusion after revascularization of an acute myocardial infarction can contribute up to 50% of the resulting infarct damage.1 Protection from reperfusion injury is an important strategy to prevent excessive damage. To date, clinical studies on reducing lethal reperfusion injury have been disappointing, despite promising preclinical data.2 To improve preclinical drug development and close the apparent translational gap, human preclinical models of ischemia/reperfusion injury may be useful. To address this challenge, we have developed a novel model system of hypoxia followed by reoxygenation in engineered human myocardium (EHM). Hypoxia-inducible factor 1 (HIF-1) is the major switch for cellular adaptation to hypoxia. Its α-subunit HIF-1α is hydroxylated by prolyl-hydroxylase domain enzymes (PHDs) at 2 conserved proline residues that are located in the oxygen-dependent degradation domain in a strictly oxygen-susceptible manner leading to rapid proteasomal degradation (Figure [A]). Hypoxia or inhibition of PHDs stabilizes the HIF-1α protein that dimerizes with ARNT (aryl hydrocarbon receptor nuclear translocator) to activate target gene transcription—promoting metabolic adaptation, cell survival, mitochondrial function, erythropoiesis, and angiogenesis.
Reference link- https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044471
