UVa Researchers Study the Cause of Atherosclerosis

Atherosclerosis happens gradually as deposits of fat, cholesterol, calcium and waste products build up in the inner lining of the arteries. Sometimes called hardening of the arteries, this disease can cause heart attack, stroke, difficulty walking, gangrene or loss of a limb.

No one can say for sure what causes atherosclerosis at the cellular level, though it’s well known that high cholesterol, cigarette smoking, high blood pressure, diabetes and obesity can contribute to it. Now, cardiovascular researchers at the University of Virginia Health System have discovered evidence that lymphoid structures may be contributing to the development of atherosclerosis because they attract a response from the body’s immune system. In the aorta, for example, in total all the lymphoid structures are about the size of one lymph node that swells when you have a cold. Lymphocytes are the main means of providing the body with immune capability. Although occasional lymphocytes are found in every normal artery wall, the organized lymphoid structures appear only in atherosclerotic arteries, the UVa researchers found. The structures play a key role in how the body routinely ‘surveys’ tissue with lymphocytes, which hunt for foreign invaders for the body to later destroy. The research is published in a paper in the May 8th issue of the Journal of Experimental Medicine. “This paper provides evidence that the immune system normally surveys large artery walls and that was not really appreciated before,” said Dr. Klaus Ley, a biomedical engineer, director of the Robert M. Berne Cardiovascular Research Center at UVa and lead author of the paper. “Why the immune system surveys them is not clear. But we can hopefully find that out. This would also explain why infectious organisms, including certain bacteria and viruses, are often found associated with atherosclerosis. The human body would mount an immune response when lymphocytes come though the arterial vessel wall.” This research at UVa was spearheaded by Elena Galkina, PhD, a native of Russia and one of the few immunologists in the world involved in the study of atherosclerosis. Galkina developed a new, more comprehensive technique in the lab to examine arterial cells using flow cytometry . Tens of thousands of cells are “flown” by a laser, which shines light of specific wavelength on each cell. A photo detector then sees fluorescently labeled antibodies, allowing scientists to find out all the molecules expressed on the surface of a cell and what type of cell it is. “Diet and obesity are still key factors in atherosclerosis,” Galkina said. “But not the only ones. If they were, Winston Churchill should not have reached the age of 90. There are other factors that we need to consider.” Ley said the next step in his research on atherosclerosis will be to manipulate the immune system to try and come up with an effective treatment to block the disease’s progression. It might be possible to make drugs targeting immune system, he said, but that is a long way away. Such drugs might also be used to augment statins, which block an enzyme in cholesterol synthesis to lower the risk of heart attack and stroke.(Source: Journal of Experimental Medicine: University of Virginia Health System: May 2006.)