Targets, trafficking, and timing of cardiac autophagy.

Heart failure is the major case of death in developed countries, and its prevalence is growing worldwide. Autophagy is a fundamental cellular mechanism through which intracellular components can be removed, recycled and repaired. Studies in humans and animal models demonstrate a marked increase in cardiac autophagic activity under a wide range of disease states and in response to diverse stimuli. Recently, autophagy has been widely promoted as a potential therapeutic target for the treatment of cardiovascular disease and heart failure. An important challenge to achieving this goal is the dual nature of cardiac autophagy, sometimes acting to help preserve cardiac function, other times appearing to promote cardiac decline. Numerous control points regulating autophagic activity and cargo selection provide a diversity of opportunities for drug targeting. In addition there is an innate circadian rhythm to the systemic regulation of autophagy that is often overlooked but provides potential opportunities to target and optimize pharmacological intervention.