Quiescent Hypervascularity Mediated by Gain of HIF-1α Function
This extract was created in the absence of an abstract.
Excerpt
CONCEPT AND CHALLENGE OFTHERAPEUTIC ANGIOGENESIS
The goal of therapeutic angiogenesis is an increase inperfusion of ischemic tissues such as the heart, limbs, andbrain. We now understand a great deal about the molecular control of angiogenesis in the context of both cell culture and animal models, and clinical trials using angiogenic growth factors or vascular precursor/stem cellshave been implemented. A novel concept is modulationof transcription factor function to affect therapeutic angiogenesis. A potential bonus of this approach is thatdownstream genetic networks regulated by the transcription factor may tailor additional cellular functions, suchas metabolism, which may facilitate ischemic adaptationand survival. Hypoxia-inducible factor-1 alpha (HIF-1α)is one transcription factor that may fulfill this promise.Not only has the molecular and cellular biology of HIF1α been extensively characterized, but molecules andsignaling pathways regulating HIF-1α protein stabilityand transcriptional activity have been identified (Semenza 2002). This body of data offers the opportunity totailor manipulation of HIF-1α function to a particular disease or condition. Recent data demonstrate that HIF-1αoverexpression can produce an increase in tissue vascularity and maintain these vessels with normal morphology and permeability. As such, manipulation of HIF-1αfunction is one mechanism to achieve therapeutic angiogenesis...
