Protein could help rejuvenate oxygen-starved cardiac tissue, heal wounds

A UCSF-led team is reporting striking results in mice that indicate that a molecule known as HIF-1α could prove an effective target for inducing the growth of blood vessels in oxygen-starved tissues. The strategy is sought for treating cardiac and peripheral vascular disease, diabetes-damaged tissues and intractable wounds.

The finding, reported in the October 1 issue of Genes & Development, is a notable advance in an effort that has met with setbacks. Researchers have tried to generate the production of healthy blood vessels by inducing over-expression of the growth factor VEGF. But studies in mice have shown that while over-expression of VEGF induces the growth of blood vessels, the capillaries are leaky, the tissues are inflamed and swollen, and the blood vessels have an abnormal corkscrew-like shape.

In the current study, researchers genetically engineered mice to overexpress the HIF-1α gene in skin cells. In response, the number of capillaries in the mices skin increased by nearly 70 percent. More importantly, the blood vessels did not leak, cause swelling or inflammation.

The vessels looked like normal capillaries, says senior author Jeffrey M. Arbeit, MD, UCSF associate professor of surgery, and a member of the UCSF Comprehensive Cancer Center. This finding, together with the fact that the vessels didn't leak, is extremely exciting. The increase in healthy blood vessels was evident in the mices significantly pinker ears, paws and tails.

Notably, in the current study the overexpression of the HIF-1α gene caused a 13-fold increase in the expression of the VEGF gene. The fact that HIF-1α had an effect on VEGF expression is not surprising in itself, as HIF-1α is a sub unit of the HIF-1 transcription factor, which regulates the expression of numerous genes, including VEGF. However, the finding does prompt the question of why the blood vessels were robust, given that previous studies involving elevate

Contact: Jennifer OBrien
University of California - San Francisco

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