4.1.3. Cardiac injury
Although altitude illnesses do not directly affect the heart, patients with cardiovascular disease may face difficulties at high altitudes. This is because physical activity at high altitudes is more oxygen-deprived than that at sea level, requiring a higher percentage of maximum heart rate and cardiac output to deliver the same amount of oxygen to the heart muscle. Impaired oxygen transport during hypoxia results in hypoxemia, which subsequently triggers a range of adaptive and maladaptive cardiovascular changes. These changes can increase the risk of stroke, myocardial injury, and thrombosis.
CYP1A1, CYP1A2, CYP1B1, CYP2C8, CYP2J2, CYP2B6, CYP4A1, CYP4B1, and CYP4F12 are expressed in the heart, and that cardiac-localized CYPs and their metabolites are cardioprotective. EETs, the epoxide oxidase metabolites of AA, not only contract cardiomyocytes and increase coronary blood flow but also promote angiogenesis, in addition to delaying or even reversing cardiac remodelling, whereas HETE has predominantly cardiotoxic effects. However, the current knowledge of the role of cardiac-specific CYPs in cardiac physiology and pathology under hypoxia is limited. Previous studies have found that the expression of cholesterol hydroxylase CYP7A1 and other enzymes involved in bile acid synthesis is reduced in hypoxic mouse models, leading to elevated cholesterol levels (Ramakrishnan et al., 2014), which are associated with the risk of cardiovascular disease. However, further research is needed to determine whether there is a direct link between the development of cardiovascular disease under hypoxia and changes in CYP. In addition, one study found that CYP expression in the heart changes under high-altitude hypoxia. Using a proteomic approach, researchers found that differentially abundant proteins in high-altitude yak heart tissue were enriched for drug metabolism (cytochrome P450) (Xin et al., 2022), further suggesting an important role of CYP in the heart during acclimation to high-altitude hypoxia.