NAVIGATING THE COMPLEXITIES OF APOPTOSIS AND AUTOPHAGY IN CARDIOVASCULAR DISEASE: CAN WE CHART A CLEAR COURSE?
Kenneth Maiese, M.D., University of Medicine & Dentistry of New Jersey, Newark, NJ, USA
The programmed cell death pathways of apoptosis and autophagy play a significant role in the reparative and regenerative processes of the cardiovascular system. Apoptosis can control tissue development and remodeling during the early stages of development. However, in mature cells the induction of apoptosis can result in cell death. In contrast, autophagy, a process that can promote cellular protection as well as cellular death involves the recycling of cytoplasmic components and discards defective organelles for tissue remodeling. Multiple pathways can ultimately influence apoptosis and autophagy in the cardiovascular system during injury, but a number of new therapeutic strategies are focusing upon the role of extracellular matrix associated proteins such as the CCN family of proteins. Of the CCN family members, Wnt1 inducible signaling pathway protein 1 (WISP1) is increasingly being recognized as an exciting target for tissue repair. WISP1 is intimately linked to pathways of regeneration that include phosphatidylinositol-3-kinase (PI 3-K), protein kinase B (Akt), and the mechanistic target of rapamycin (mTOR). Elucidating the potential of these novel reparative pathways and the ability to govern apoptosis and autophagy offers new hope for the treatment of acute and chronic disorders of the cardiovascular system.