INSIGHT FROM POPULATIONS DWELLING AT HIGH ALTITUDE
Hypoxia can also serve as a model for certain adaptations that create
resilience to disease but this can only be studied by an experiment of
nature. For example, studying high-lander populations has revealed a
number of genes that allow for adaptation to chronic hypoxia [47].
These groups, such an Andean’s, Ethiopians, and Tibetans have evolved
variations in their erythrocyte homeostasis, angiogenesis,
vaso-regulation, cell death, immune response, cognition, and various
other processes that are often implicated in disease. The aforementioned
populations had adapted a lower expression of the gene EDNRB, which has
a large regulatory region of single-nucleotide polymorphisms and
transcription binding sites [48]. Mice with this gene knocked out
showed extreme hypoxia tolerance [49]. Congruently, patients with
ischemic heart disease show significantly higher levels of EDNRB and
antagonists of this gene are used to reduce induced high-altitude
pulmonary artery pressure [50, 51]. All of this evidence supports
this highlander adaptation as a valuable model for cardiac disease. Such
studies have also identified key epigenetic shifts that require further
mechanism investigation. Despite the promising translational model of
highlanders, studying these groups has its limitations; they are
difficult to access and have been isolated for long enough to have
accrued hypoxia-unrelated and thus confounding genetic differences. This
emphasizes the need to categorize variations in hypoxia related
adaptations amongst the general population as well as investigate how
easily inducible these epigenetic changes are for possible therapeutic
intervention.