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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Boutin, Adam T. Goldrath, Ananda W. Kim, Jung-whan Sterling, Jane C. Nakasaki, Manando Cowburn, Andrew S. Chilvers, Edwin R. Takeda, Norihiko Jamora, Colin Nizet, Victor Southwood, Mark Johnson, Randall S. |
| Description | Author Affiliation: Cowburn AS ( Departments of Physiology, Development and Neuroscience and Medicine, University of Cambridge CB2 3EG, Cambridge, United Kingdom.); |
| 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-1 and HIF-2 , 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-1 and HIF-2 expression in keratinocytes is a control element of both tissue perfusion and systemic arterial pressure, with potential implications in human hypertension. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 43 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Arterial Pressure Physiology Basic Helix-Loop-Helix Transcription Factors Metabolism Hypoxia-Inducible Factor 1, Alpha Subunit Skin Blood Supply Animals Arginase Genetics Blotting, Western Hypertension Drug Therapy Physiopathology Immunohistochemistry Keratinocytes Cytology Mice Mice, Inbred C57BL Mice, Knockout Nitric Oxide Synthase Type II Nitric Oxide Synthase Type III Regional Blood Flow Reverse Transcriptase Polymerase Chain Reaction Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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