Conclusion
Exposure of the adult mammalian pulmonary circulation to alevolar
hypoxia triggers rapid onset vasoconstriction and subsequent structural
remodelling, co-ordinated through an integrated series of molecular
events. Genetic studies in humans and animals coupled with genetically
manipulated animal models have the potential to elucidate the conductors
of this ”orchestra”. HIF-2α (encoded by EPAS1 ), PHD2 (encoded byEGLN1 ) and ZIP12 provide proof-of-concept for this strategy,
although translating this into a new drug therapy for pulmonary
hypertension remains to be demonstrated. Moreover, these studies provide
more insight into the vascular remodelling than the vasoconstrictor
component of the hypoxic response. Perhaps not surprising, phenotype
studies of residents at high altitude have focused more on accessible
physiological characteristics, such as haemoglobin and oxygen
saturation, than more challenging measurements, such as pulmonary
physiology. Such data remain few. The potential rewards give fresh
impetus to the need for further detailed genotype-phenotype studies
addressing pulmonary vascular adaptation of high altitude residents.
Competing Interests: None