To date, the drug sulindac has seen two primary uses: treating such inflammatory diseases as rheumatoid arthritis and preventing the growth of potentially precancerous colon polyps. But in today¿s Proceedings of the National Academy of Sciences, researchers from New York report yet another indication: sulindac may help prevent the narrowing of arteries after angioplasty¿a procedure that involves widening blood vessels blocked by atherosclerosis using a tiny balloon or stent. Angioplasty works well in the short term, but it can injure the artery wall. In these cases, the injury probably leads to an inflammatory response, which in turn stimulates the growth of smooth muscle cells that narrow the vessel all over again.
To test sulindac's effects in mice, the authors injured an artery in the upper leg of the animals using a procedure similar to angioplasty and then gave sulindac to some animals, aspirin to others and no treatment to a third group. After four weeks, they found that mice receiving sulindac showed considerably less thickening of their artery walls than the others. The effect was even more pronounced in mice that, as the result of a genetic defect, had very high blood cholesterol levels. (Most patients who undergo angioplasty also have high blood cholesterol levels.) These mice, when untreated, showed more than twice as much wall thickening as normal mice. Yet after treatment with sulindac, their arterial walls were the same size as those of normal mice receiving the drug.
The reasearchers do not know why sulindac worked and aspirin did not. Both are nonsteroid, anti-inflammatory agents, known to inhibit an enzyme called cyclooxygenase. The only guess so far is that sulindac might have additional effects, including inhibiting macrophages, or the growth of smooth muscles cells or endothelial cells. Whatever the mechanism, sulindac might help people who have undergone angioplasty avoid having their arteries clog up again.
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