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Another way to grow blood vessels
Date:2/20/2008

BOSTONResearchers at Dana-Farber Cancer Institute have found a previously unknown molecular pathway in mice that spurs the growth of new blood vessels when body parts are jeopardized by poor circulation.

At present, their observation adds to the understanding of blood vessel formation. In the future, though, the researchers suggest it is possible that the pathway could be manipulated as a means of treating heart and blood vessel diseases and cancer. The paper appears in the Feb. 21 issue of the journal Nature.

Bruce Spiegelman, PhD, and his colleagues at Dana-Farber discovered that PGC-1alpha a key metabolic regulatory molecule senses a dangerously low level of oxygen and nutrients when circulation is cut off and then triggers the formation of new blood vessels to re-supply the oxygen-starved area a process known as angiogenesis.

A similar response to hypoxia, or oxygen deprivation, has been observed before. The response is regulated by a group of proteins known as Hypoxia Inducible Factors (HIF) that detect hypoxia and activate the production of VEGF (vascular endothelial growth factor). VEGF, in turn, stimulates angiogenesis.

The newly discovered pathway provides an independent way of getting there, says Spiegelman, who is also a professor of cell biology at Harvard Medical School. Along with lead author Zoltan Arany, MD, PhD, and colleagues, Spiegelman found that HIF was completely left out of the loop when PGC-1alpha accomplished the same feat in single cells and in live mice using a different regulator, known as ERR-alpha (estrogen-related receptor-alpha).

When the scientists knocked out the activity of PGC-1 alpha (which was first identified in the Spiegelman lab) in cells and live mice, the hypoxia-induced response and angiogenesis were sharply decreased.

We were surprised to find this novel mechanism, comments Spiegelman.

It was apparently there all along, adds Arany. That means there is now
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert

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