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