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 remodellingļ¼ 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.