Research: Atherosclerosis is a disease in which plaques made up of fat, cholesterol, calcium, and other substances build up inside arteries. The build up of these plaques and/or their rupture can lead to occlusion of arteries resulting in conditions such as myocardial infarction and stroke. In the end stages of the pathological process of atherosclerosis, perivascular cells differentiate into osteoblast-like cells and begin to lay down bony matrix. This leads to stiffening of the arteries and progression of atherosclerosis from fatty streaks to rupture-prone plaques. The dangers of calcification are underscored by recent findings that coronary artery calcification has been shown to be a more accurate predictor of clinical risk for cardiovascular disease mortality than any other epidemiological measure. Preventing the osteogenic differentiation of perivascular cells represents a potential means of halting the progression of atherosclerosis. The primary cilium is an important signaling organelle present on most cells of the body during the growth (G1) or growth arrested (G0) phase of the cell cycle. Interestingly, endothelial and perivascular cells of healthy vasculature do not have primary cilia, while endothelial and perivascular cells in areas of disturbed flow and atherosclerotic plaques do. Thus, primary cilia represent hallmark of the atherosclerotic pathology. My work seeks to show that disruption of primary cilia can prevent osteogenic differentiation of these perivascular cells and halt the progression of atherosclerosis
Conferences:
McGowan Institute for Regenerative Medicine, 3/6/2013.