"For years, we've heard people say, 'Bad metabolism runs in my family,'" says Clay F. Semenkovich, M.D., professor of medicine and of cell biology and physiology. "Our study suggests 'bad' metabolism does lead to inflammation in blood vessel walls and can contribute to heart attacks and strokes."

Smoking and elevated cholesterol levels have been shown to increase vascular disease, but these risk factors are absent in many cases. Reporting this week in the journal Nature, Semenkovich and colleagues offer evidence of another mechanism behind atherosclerosis. Traditionally, scientists have thought of atherosclerosis as a chronic inflammation that results from vascular injury. But these studies suggest the root cause may be mitochondrial problems in the cells of the blood vessel wall. Semenkovich says the findings provide scientists with new targets for treating vascular disease.

The researchers studied mice genetically engineered to overproduce a protein in the wall of the aorta, the body's primary artery. When made in skeletal muscle, the protein, called uncoupling protein-1, protects mice from diabetes and obesity. Uncoupling protein converts the energy from food into heat and, in skeletal muscle, mimics the effects of exercise.

The researchers thought if the mice made uncoupling protein-1 in their blood vessel walls, it might protect them from atherosclerosis and high blood pressure.

"Our original hypothesis was wrong," says Semenkovich, who directs the School of Medicine's Division of Endocrinology, Metabolism and Lipid Research and is a staff physician at Barnes-Jewish Hospital. "When we made mice that produced uncoupling protein in the aorta, we were amazed because rather than being protected from da
'"/>

Contact: Jim Dryden
jdryden@wustl.edu
314-286-0110
Washington University School of Medicine
25-May-2005