Making new veins

September 30, 2001

Scientists at UCSF have discovered the most effective way, to date, to generate healthy new blood vessels - a discovery with important therapeutic implications for the treatment of cardiac and peripheral vascular disease, diabetes and recalcitrant wounds.

As published in Genes & Development, Dr. Jeffrey Arbeit and colleagues have discovered that the continuous expression of a single gene, HIF-1a, can induce the formation of new blood vessels in mice. The HIF-1a protein comprises one subunit of the hypoxia-inducible factor-1 (HIF-1) protein. HIF-1 regulates the activity of several genes which promote angiogenesis in response to oxygen deprivation.

Dr. Arbeit and colleagues generated a strain of mice that continuously express the human HIF-1a gene specifically in epidermal cells, and therefore always have high levels of active HIF-1 in their skin. Under normal oxygen conditions, these HIF-1a transgenic mice display such a marked increase in skin capillary formation that it is noticable to the naked eye (see figure).

As oxygen deprivation, or ischemia, is a common symptom of many different diseases and injuries, there have been several previous attempts to generate new blood vessels. None has ever been this successful.

Previous attempts have centered upon the over-expression of a downstream target of HIF-1, named VEGF. VEGF is a growth factor that is important for the formation of new blood vessels. Although over-expression of VEGF does induce angiogenesis, the resultant vessels are leaky and are associated with sever edema and inflammation. Dr. Arbeit and colleagues demonstrate that HIF-1a-induced vasculature is structurally indistinguishable from normal vasculature and is not associated with any of these undesirable side effects. In light of this recent discovery, HIF-1a now stands as a strong candidate for tissue ischemia therapy.

Cold Spring Harbor Laboratory

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