Myxomatous Mitral Valve Disease: The Importance of Senescence, Apoptosis and Autophagy

Presentation Description / Summary: Understanding the cause of myxomatous mitral valve disease (MMVD) is required before any new treatments can be discovered. MMVD is the most common acquired cardiovascular disease of the dog and is a very good example of an age-related degenerative condition in our patients. The acquisition of cell senescence (permanent cell growth arrest) is a cardinal feature of degenerative diseases and is associated with changes in the apoptotic and autophagy mechanisms necessary to remove cells and cellular debris from damage tissues. Similar changes are also found in other degenerative diseases and various cancers. Evidence is emerging of the importance of cell senescence in the development of a range of human cardiovascular diseases and associated disease models, and with that changes in a selective form of autophagy know as mitophagy necessary for the removal of dysfunctional mitochondria. These exciting discoveries point to common mechanisms of chronic disease pathogenesis that are targets for novel drug therapy, and increase the chances that treatments to prevent, arrest or even reverse valve degeneration in MMVD will be possible. This lecture will examine the mechanisms of senescence, apoptosis and autophagy relevant to MMVD and other valvulopathies in the dog and human and critically evaluate the evidence supporting their contribution to valve disease development. The methods by which such dysfunctional mechanisms likely result in aberrant valve tissue remodeling, comparisons with other degenerative diseases and cancers, and how these novel findings impact of development of novel treatments will be explored and discussed.