Endothelin receptor B, a candidate gene from human studies at high altitude, improves cardiac tolerance to hypoxia in genetically engineered heterozygote mice.

ABSTRACT: To better understand human adaptation to stress, and in particular to hypoxia, we took advantage of one of nature's experiments at high altitude (HA) and studied Ethiopians, a population that is well-adapted to HA hypoxic stress. Using whole-genome sequencing, we discovered that EDNRB (Endothelin receptor type B) is a candidate gene involved in HA adaptation. To test whether EDNRB plays a critical role in hypoxia tolerance and adaptation, we generated EdnrB knockout mice and found that when EdnrB (-/+) heterozygote mice are treated with lower levels of oxygen (O2), they tolerate various levels of hypoxia (even extreme hypoxia, e.g., 5% O2) very well. For example, they maintain ejection fraction, cardiac contractility, and cardiac output in severe hypoxia. Furthermore, O2 delivery to vital

SUBMITTER: Stobdan T 

PROVIDER: S-EPMC4547246 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature