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Physiology in Press

First published online on August 24, 2007.
Experimental Physiology (2007)
DOI: 10.1113/expphysiol.2006.036343
© The Physiological Society 2007
A more recent version of this article appeared on November 1, 2007
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Received May 17, 2007
Revised July 13, 2007
Accepted after revision August 16, 2007

Vascular [310]

Regulation of Tissue Perfusion by Hypoxia-Inducible Factor 1

Gregg L. Semenza 1*

1 The Johns Hopkins University School of Medicine

* To whom correspondence should be addressed. E-mail: gsemenza{at}jhmi.edu.


  Abstract
The regulation of tissue perfusion is a major mechanism by which oxygen homeostasis is maintained. Hypoxia-inducible factor 1 (HIF-1) is a transcriptional regulator that mediates adaptive responses to reduced PO2 in all metazoan species. In mammals, HIF-1 promotes angiogenesis, arteriogenesis, and vasculogenesis through the production of multiple angiogenic growth factors in ischemic tissue and by cell-autonomous effects on endothelial cells and bone marrow-derived angiogenic cells. Administration of viral vectors encoding constitutively-active forms of the HIF-1a subunit result in increased tissue perfusion in animal models of ischemic cardiovascular disease.

Key Words: Hypoxia, Ischaemia, Vascular blood flow




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