Research ArticlePhysiology

The LKB1–AMPK-α1 signaling pathway triggers hypoxic pulmonary vasoconstriction downstream of mitochondria

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Science Signaling  02 Oct 2018:
Vol. 11, Issue 550, eaau0296
DOI: 10.1126/scisignal.aau0296

Hypoxia amps AMPK

Most arteries in the body vasodilate in response to hypoxia. In contrast, pulmonary arteries constrict in response to hypoxia to ensure that blood is diverted to oxygen-rich areas, a process called hypoxic pulmonary vasoconstriction. When this process is prolonged, it can lead to pulmonary hypertension and, ultimately, heart failure. Analysis of genetically manipulated mice by Moral-Sanz et al. showed that hypoxic pulmonary vasoconstriction under mild hypoxia required the α1 subunit of AMPK, which was activated downstream of LKB1 during hypoxia. During severe hypoxia, the α2 subunit of AMPK was also required. AMPK supports hypoxic pulmonary vasoconstriction, in part, by phosphorylating and inhibiting the K+ channel KV1.5 in pulmonary arterial myocytes. By contrast, in most systemic arteries, hypoxia does not inhibit KV, which may aid vasodilation rather than vasoconstriction. These results delineate a key role for LKB1-activated AMPK-α1 and AMPK-α2 in hypoxic pulmonary vasoconstriction.

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