Prolonged exposure to high altitude with reduced partial pressure of oxygen in the atmosphere has protective effects on heart function. Under hypoxia, heart cells express proteins such as HIF-1α to activate specific genes and start molecular mechanisms to protect themselves. New results from the Laboratory of Developmental Cardiology at the Institute of Physiology of the CAS reveal that the presence of the HIF-1α is crucial for active removal of dysfunctional or redundant mitochondria, the cell’s energy factories. Hence, a new cellular mechanism that helps to protect the heart from the consequences of acute myocardial infarction has been uncovered.
To investigate the underlying mechanism, our team conducted a study with mice that were either regular (wild-type) or had lower levels of the HIF-1α protein. Some mice were exposed to chronic hypoxia for four weeks, while others stayed in normal oxygen conditions. Their hearts underwent ischemia/reperfusion insult, mimicking the process of a myocardial infarction and recovery.
We found that mice exposed to low oxygen had stronger hearts that resisted damage better than those that did not have this adaptation. Interestingly, we also showed that the heart cells of these mice showed important changes. They actively cleared out damaged mitochondria, the cell’s “energy factories”, in a process called mitophagy, to stay healthy. These adaptive changes did not occur in mice with decreased levels of HIF-1α protein. To see if this “self-cleaning” process was essential, we blocked mitophagy in some mice. When we did, the beneficial effect disappeared, and the hearts were no longer protected, suggesting that mitophagy is crucial for the protective role of HIF-1α. This research gives us a better understanding of how HIF-1α promotes healthy energy processes in cells under stress. It paves the way for new treatments that might help the heart better withstand oxygen shortages in patients with ischemic heart disease.
Reference: Alanova P. et al.: HIF-1α limits myocardial infarction by promoting mitophagy in mouse hearts adapted to chronic hypoxia. Acta Physiol (Oxf). 2024 Sep;240(9):e14202. DOI
