HIF isoforms in the skin differentially regulate systemic arterial pressure.
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.
['Cowburn|Andrew S|AS|', 'Takeda|Norihiko|N|', 'Boutin|Adam T|AT|', 'Kim|Jung-Whan|JW|', 'Sterling|Jane C|JC|', 'Nakasaki|Manando|M|', 'Southwood|Mark|M|', 'Goldrath|Ananda W|AW|', 'Jamora|Colin|C|', 'Nizet|Victor|V|', 'Chilvers|Edwin R|ER|', 'Johnson|Randall S|RS|']
D000328:Adult D000368:Aged D000818:Animals D001119:Arginase D062186:Arterial Pressure D051792:Basic Helix-Loop-Helix Transcription Factors D015153:Blotting, Western D005260:Female D006801:Humans D006973:Hypertension D051795:Hypoxia-Inducible Factor 1, alpha Subunit D007150:Immunohistochemistry D015603:Keratinocytes D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D008875:Middle Aged D052247:Nitric Oxide Synthase Type II D052250:Nitric Oxide Synthase Type III D012039:Regional Blood Flow D020133:Reverse Transcriptase Polymerase Chain Reaction D012867:Skin D055815:Young Adult
HIF-alpha arginase vascular tone