Hearts That Refuse to Mend

Some heart disease patients may not be able to grow new blood vessels around blocked arteries because they can't make enough of a vital protein, according to a report in the latest issue of Circulation. If confirmed by larger trials, the finding could lead to a diagnostic test that will help cardiologists identify and treat high-risk patients.

When an artery supplying blood to the heart becomes clogged, the vessel can sometimes build an alternate route around the backup, a process called angiogenesis. But only about half of all patients are able to grow these new vessels.

Suspecting that a difference in expression of the VEGF gene might account for the varying ability of the heart to build its own bypass vessels, Andrew Levy and his colleagues at the Technion-Israel Institute of Technology in Haifa, Israel, used angiography pictures to rank 51 heart disease patients into three groups, based on the number of new blood vessels their arteries had grown in response to a clog. They then measured a patient's VEGF expression by harvesting blood cells called monocytes, which are believed to be involved in angiogenesis. A low-oxygen environment--comparable to a vessel wall not receiving enough blood--caused cells from patients with a high angiogenesis score to make more than three times as much VEGF RNA.

So VEGF levels appear to provide a good way of measuring whether a patient will be able to grow these new blood vessels, says Levy, and his group is hoping to develop a VEGF blood test that will help cardiologists know how best to treat their patients. If a patient is able to make more VEGF, "that would indicate we could treat more conservatively with medicines," whereas those who made little VEGF might be better candidates for bypass surgery, he says.

"The potential diagnostic applications are exciting, but a great deal more work needs to be done," says William Li, president and medical director of the Angiogenesis Foundation in Cambridge, Massachusetts. Most important, the study needs to be repeated with a larger patient group, he says, but adds that the researchers can't yet rule out the possibility that some patients may not make enough VEGF receptors. He says the findings are also of crucial importance to Genentech and other biotech companies now conducting clinical trials of VEGF therapy.

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