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.
journal_name
Proc Natl Acad Sci U S Aauthors
Cowburn AS,Takeda N,Boutin AT,Kim JW,Sterling JC,Nakasaki M,Southwood M,Goldrath AW,Jamora C,Nizet V,Chilvers ER,Johnson RSdoi
10.1073/pnas.1306942110subject
Has Abstractpub_date
2013-10-22 00:00:00pages
17570-5issue
43eissn
0027-8424issn
1091-6490pii
1306942110journal_volume
110pub_type
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