Chapter 13 - Autophagy in Atherosclerosis

Abstract

Atherosclerosis is a long-term inflammatory disease of the arterial wall, characterized by the formation of atherosclerotic plaques, and is still the leading cause of death in the Western world. Autophagy is a subcellular process for the degradation of long-lived proteins and dysfunctional or damaged organelles. Under stress conditions, autophagy is upregulated and serves as a cell survival mechanism through nutrient recycling and the generation of energy. A growing body of evidence indicates that autophagy occurs in all major cell types in atherosclerotic plaques and is stimulated by reactive oxygen species, oxidized lipids, inflammatory mediators, and metabolic stress to safeguard plaque cells from apoptosis. Advanced atherosclerotic plaques, however, show several features of defective autophagy, which may compromise plaque stability by increasing macrophage apoptosis and accelerating vascular smooth muscle cell senescence. Therefore, pharmacological therapies that stimulate the pro-survival effects of autophagy are promising new treatment options to delay atherosclerotic plaque progression and to promote plaque stabilization. In this chapter, we discuss the role of autophagy in atherosclerosis and underline the challenging aspects of detecting autophagy in human and experimental atherosclerotic tissue. Moreover, we give an overview of the currently known pharmacological approaches to stimulate autophagy and discuss their therapeutic potential in the treatment of atherosclerotic disease.