Grant: Project Grant

Calcification of arteries occurs in more than 1/2 of the population over the age of 60, and causes significant morbidity and mortality in diseases like atherosclerosis, diabetes, hypertension and in chronic kidney disease. Smooth muscle cells within the arteries deposit minerals in the extracellular matrix, in a process similar to the mineralization and hardening of bones, and this causes thickening, stiffening and sometimes rupture of these vessels. At present, there are no effective medical treatments to prevent or reverse calcification. Furthermore, calcified vessels cannot be angioplastied or stented, the two most common and successful treatments for atherosclerosis and peripheral vascular disease. We have recently discovered that a receptor protein which is expressed on arterial smooth muscle cells is responsible for calcification. This receptor, DDR1, causes a switch in the smooth muscle cells so that they start to behave like bone cells, and deposit minerals (calcifications) in the tissue. We seek to better understand the role of DDR1 in these processes during atherosclerosis, and the consequences for normal function of blood vessels. Importantly, we will test a new inhibitor for DDR1 in a mouse model of atherosclerosis, to see if we can inhibit calcification. Most or our work to date has been performed in tissue culture and mouse models. We will now for the first time investigate the expression and function of DDR1 in human diseased arteries. Our hope is that the work will lead to the development of new therapies designed to inactivate DDR1 and therefore prevent the calcification of arteries.