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Targeting hypoxia-inducible factor 1 to stimulate tissue vascularization

Gregg L Semenza
DOI: 10.1097/JIM.0000000000000206 Published 28 January 2016
Gregg L Semenza
Institute for Cell Engineering, Department of Pediatrics, Medicine, Oncology, Radiation Oncology, and Biological Chemistry, and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Abstract

When tissue perfusion is impaired, the resulting reduction in O2 availability activates hypoxia-inducible factor 1 (HIF-1), which mediates increased transcription of genes encoding multiple angiogenic factors including vascular endothelial growth factor, stromal-derived factor 1, placental growth factor, and angiopoietins, leading to the mobilization of bone marrow-derived angiogenic cells, increased angiogenesis, and arterial remodeling. These HIF- 1-dependent responses are impaired by aging or loss of function mutations at the locus encoding the HIF-1α subunit. in mouse models of limb ischemia and lung transplant rejection, the augmentation of HIF-1 activity by gene therapy or chemical inducers was associated with maintenance of tissue perfusion that prevented limb amputation and allograft rejection, respectively. Thus, targeting HIF-1 may be of therapeutic benefit in these clinical contexts and others in which impaired tissue perfusion plays a role in disease pathogenesis.

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Vol 64 Issue 2 Table of Contents
Journal of Investigative Medicine: 64 (2)
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Targeting hypoxia-inducible factor 1 to stimulate tissue vascularization
Gregg L Semenza
Journal of Investigative Medicine Feb 2016, 64 (2) 361-363; DOI: 10.1097/JIM.0000000000000206

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Targeting hypoxia-inducible factor 1 to stimulate tissue vascularization
Gregg L Semenza
Journal of Investigative Medicine Feb 2016, 64 (2) 361-363; DOI: 10.1097/JIM.0000000000000206
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Targeting hypoxia-inducible factor 1 to stimulate tissue vascularization
Gregg L Semenza
Journal of Investigative Medicine Feb 2016, 64 (2) 361-363; DOI: 10.1097/JIM.0000000000000206
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    • Abstract
    • HIF-1 MEDIATES ISCHEMIA-INDUCED VASCULAR REMODELING IN A MOUSE MODEL OF CRITICAL LIMB ISCHEMIA
    • HIF-1 IS REQUIRED FOR PRESERVATION OF ALLOGRAFT MICROVASCULATURE IN A MOUSE MODEL OF LUNG TRANSPLANTATION
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