Study Findings May Lead To Earlier Diagnosis And Treatment Of Atherosclerosis

November 11, 1997

PITTSBURGH, Nov. 11 -- Earlier diagnosis and treatment of atherosclerosis may be possible using specially engineered, gas-filled microbubbles, according to a study by researchers at the University of Pittsburgh Medical Center (UPMC).

The study will be presented Nov. 11 by Flordeliza S. Villanueva, M.D., assistant professor of medicine in the division of cardiology, at the annual scientific session of the American Heart Association in Orlando, Fla.

Microbubbles, gas-filled microspheres the size of red blood cells, are used in contrast echocardiography, an ultrasound technique used to detect blood flow to the heart muscle in conditions such as angina or heart attack.

One of the first processes leading to atherosclerosis involves the inflammation of the endothelial cells which line blood vessels. The researchers wanted to find a way to identify these abnormal endothelial cells which are harbingers of atherosclerosis. To simulate the inflammation which occurs on endothelial cells during early atherosclerosis, cultured endothelial cells were experimentally stimulated to produce a protein on their surface called ICAM-1. ICAM-1 is thought to be centrally involved in the development of atherosclerosis.

"Currently, we have no techniques for identifying this potentially reversible, major change in endothelial cells in humans," Dr. Villanueva said.

The study, performed in collaboration with William Wagner, Ph.D., assistant professor of surgery and chemical engineering at the UPMC's McGowan Center for Artificial Organ Development, attempted to develop contrast echocardiography as a method to study this very early abnormality which occurs in patients who subsequently develop coronary artery disease.

In their study, the researchers cultured human coronary artery endothelial cells on lab coverslips. Three types of microbubbles were made; one containing anti-human ICAM-1 monoclonal antibody, one with non-specific murine immunoglobulin, and one with no added proteins.

Some of the endothelial cells were stimulated by interleukin-1 while others were not. Both groups were then exposed to one of the microbubble preparations. Researchers then counted the number of microbubbles which bound to the endothelial cells.

According to the study, binding of microbubbles to normal endothelial cells was minimal, however, there was a 40-fold increase in adherence of the microbubbles containing anti-ICAM-1 to the activated endothelial cells. These adherent microbubbles can then be detected using ultrasound imaging (echocardiography).

"This may allow us to localize an area of the artery where atherosclerosis is just developing so that we can intervene at a much earlier disease stage than is currently possible," said Dr. Wagner.

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University of Pittsburgh Medical Center

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