Grant: Operating Grant

Cardiovascular diseases (infarct and stroke) remain the main causes of death in Canada. A typical feature of vascular diseases is the calcification of blood vessels, i.e. the formation of bony material in the circulation system. Calcification makes blood vessels brittle and affects blood flow. Interestingly, there is a strong correlation between osteoporosis, the loss of bone, and the formation of mineral deposits in arteries. Arterial calcification is predictive of cardiovascular mortality and is tightly associated with aging and arterial remodeling. Calcification happens in particular in the extracellular matrix of blood vessels. The main extracellular matrix components, elastin and collagen, are both heavily degraded by cathepsins during the hardening of arteries (atherosclerosis) but also during the balooning of blood vessels (aneurisms). However little is known about the mechanism of calcification and whether the degradation of the matrix leads to mineralization or vice versa and whether the calcification is a kind of protective but out of control response to the vessel destruction. One protease, cathepsin K, is of particular interest as we and others have demonstrated that this enzyme is critically involved in the weakening of arteries and at the same time responsible for bone degradation. Efforts are underway to introduce a cathepsin K inhibitor for the treatment of osteoporosis to the market. We predict that this inhibitor will be highly beneficial to prevent arterial degradation and calcification as well. Thus, our objectives are to understand the role of cathepsins in arterial calcification and to device strategies to treat cardiovascular diseases.