Grant: Travel Awards - Institute Community Support

Cardiovascular diseases remain the main causes of death in industrialized countries and especially in North America. A common complication of vascular diseases is the calcification of blood vessels, i.e. the formation of bone-like minerals in the circulatory system. Calcification makes blood vessels brittle and affects blood flow. Arterial calcification is a strong marker of cardiovascular mortality and is tightly associated with aging and arterial remodeling. Calcification occurs in particular in the extracellular matrix of blood vessels, especially in damaged area. The main extracellular matrix components, elastin and collagen, are both heavily degraded by cathepsins during the hardening of arteries (atherosclerosis). However little is known about the mechanism of calcification and whether the degradation of the matrix leads to mineralization or whether the calcification constitutes a protective but out of control response to the vessel destruction. Human cysteine protease cathepsins (Cat) K, S and V are of particular interest as we and others have demonstrated that these enzymes are critically involved in the weakening of arteries associated with the formation of the atheroma plaque. Our objectives are to understand the role of cathepsins in arterial calcification and to device strategies to treat cardiovascular diseases. In our latest study we demonstrated that the degradation of elastin by catK, S and V increases its calcification and conversely, calcified elastin was more resistant to degradation. Moreover, the cleavage of elastin by these three enzymes releases fragments that can act on the cells constituting the vessels wall. These elastin fragments stimulate the production of mineral matrix by vascular cells.