HIF isoforms in the skin differentially regulate systemic arterial pressure.

Abstract:

:Vascular flow through tissues is regulated via a number of homeostatic mechanisms. Localized control of tissue blood flow, or autoregulation, is a key factor in regulating tissue perfusion and oxygenation. We show here that the net balance between two hypoxia-inducible factor (HIF) transcription factor isoforms, HIF-1α and HIF-2α, is an essential mechanism regulating both local and systemic blood flow in the skin of mice. We also show that balance of HIF isoforms in keratinocyte-specific mutant mice affects thermal adaptation, exercise capacity, and systemic arterial pressure. The two primary HIF isoforms achieve these effects in opposing ways that are associated with HIF isoform regulation of nitric oxide production. We also show that a correlation exists between altered levels of HIF isoforms in the skin and the degree of idiopathic hypertension in human subjects. Thus, the balance between HIF-1α and HIF-2α expression in keratinocytes is a control element of both tissue perfusion and systemic arterial pressure, with potential implications in human hypertension.

authors

Cowburn AS,Takeda N,Boutin AT,Kim JW,Sterling JC,Nakasaki M,Southwood M,Goldrath AW,Jamora C,Nizet V,Chilvers ER,Johnson RS

doi

10.1073/pnas.1306942110

subject

Has Abstract

pub_date

2013-10-22 00:00:00

pages

17570-5

issue

43

eissn

0027-8424

issn

1091-6490

pii

1306942110

journal_volume

110

pub_type

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