Research

Research

Urokinase is Not Benign in Blood Vessels

A substance for treating blood clots may also be involved in atherosclerosis, according to an article published in the August 2002 issue of the Proceedings of the National Academy of Sciences. A team led by Dr. David Dichek, professor of medicine and holder of the John L. Locke, Jr. Family Endowed Chair in Cardiovascular Research and Treatment, reported that elevated levels of plasminogen activator, or urokinase, can cause constrict blood vessels and can accelerate atherosclerosis.


	Cells clog a blood vessel.

Urokinase is a naturally occurring protein in the human body. The substance is typically used as a therapeutic agent to dissolve blood clots blocking arteries. A potential side effect of all clot-dissolving agents is excessive bleeding.

Initially researchers thought a gene-therapy strategy could be developed to over-express urokinase to prevent blood clot formation in the vessels of atherosclerotic patients. Dichek's previously had looked at the effect of genetic over-expression of urokinase during an hour-long experiment. In this earlier study, blood clot formation was inhibited by urokinase overexpression.

In the latest study, researchers looked at the result of two weeks of increased expression of urokinase on the carotid arteries of cholesterol-fed rabbits. Four weeks after gene transfer, the inner lining of the rabbits' artery walls had thickened by about 70 percent compared to arteries of rabbits in the control group. The arteries in the experimental group were significantly narrowed.

Although urokinase no longer appears to be a candidate for gene therapy to combat atherosclerosis, Dichek noted that this research helps to better understand the processes that lead to atherosclerosis.

"This is a nice example of how gene-therapy research can advance our understanding of diseases, even when it doesn't produce an immediate cure," said Dichek. "Gene therapy has received some bad press lately. However, if one proceeds slowly and carefully, one can gain useful information even when the results are negative."

Dichek and his group are taking insights from this study to modify urokinase to a form that they believe will dissolve blood clots without thickening blood vessel walls.