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Researchers Uncover Process Leading to Arterial Plaque Rupture

Findings may be key to alternative therapies to prevent strokes, heart attacks

WEDNESDAY, Dec. 13, 2006 (HealthDay News) -- An important molecular process that can cause plaque rupture in people with atherosclerosis has been identified by Columbia University Medical Center researchers.

The findings could lead to therapies to prevent plaque rupture, which can produce clots that may block blood flow and cause heart attacks and strokes.

The Columbia team identified what causes the death of macrophages, which are white blood cells that accumulate in the cholesterol-laden plaques on the inside of arteries. These dead macrophages, which collect into a "macrophage graveyard," are an important cause of plaque rupture.

This study found that macrophages in the plaques die when two receptors on the cell's surface -- TLR4 and SRA -- are activated at the same time. When it's activated alone, TLR4 keeps the macrophage alive. However, when SRA is activated at the same time, it shuts down TLR4, leading to the death of the macrophage.

The findings were published Dec. 11 in the journal Proceedings of the National Academy of Sciences.

Until recently, scientists had hoped that drugs that increase "good" HDL cholesterol, used in combination with statins that reduce "bad" LDL cholesterol ,might help treat atherosclerosis patients. However, the recent failure of an experimental drug designed to increase HDL levels suggests that it may not be possible to rely solely on drugs that raise HDL levels to prevent plaque rupture.

"The recent failure of an HDL boosting therapy means it's particularly important for us to consider alternative strategies and to understand the process behind the rupture of plaques," Dr. Ira Tabas, professor of medicine and anatomy and cell biology, said in a prepared statement.

"Our hope is that this research will lead to alternative therapies to prevent plaque rupture and resulting strokes and heart attacks," said Tabas, who is also Richard J. Stock Professor and vice chairman of research at Columbia University Medical Center.

More information

The U.S. National Heart, Lung, and Blood Institute has more about atherosclerosis.

Columbia University Medical Center, news release, Dec. 11, 2006
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