HIF-1(alpha)CA5: A Stable and Constitutively-Active Form of HIF-1(alpha)

Technical Overview:
 
Animals and people are dependent on a continuous supply of O(2) for survival. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in development, physiology, and disease.  Vascularization and vascular remodeling represent critical adaptive responses to tissue hypoxia that are mediated by HIF-1. In patients with peripheral arterial disease, these responses are impaired by aging and diabetes, leading to critical limb ischemia and amputation. 
 
JHU researchers have engineered a constitutively active form of HIF-1α called HIF-1αCA5 that is resistant to O2-dependent degradation and which can be used to study HIF-1 related responses and mechanisms. Two such uses of HIF-1αCA5 include:

• Intramuscular injection of HIF-1αCA5 increases the recovery of blood flow following femoral artery ligation in a mouse model of age-dependent critical limb ischemia.
• Intradermal injection of HIF-1αCA5 promotes healing of cutaneous wounds in a mouse model of diabetes.

  
Publication(s):

1. Annals of the New York Academy of Sciences. 2009 Oct 1;1177(1):2-8.
2. J Cell Physiol. 2008 Nov; 217(2): 319–327.
3. J Biol Chem. 2008 Apr 18; 283(16): 10892–10903 

 
 

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