Autophagy in atherosclerosis

Abstract

Autophagy is a catabolic pathway for bulk destruction of long-lived proteins and organelles via lysosomes. Basal autophagy represents a reparative, life-sustaining process, but unrestrained autophagic activity promotes cell death. A growing body of evidence suggests that autophagy occurs in advanced atherosclerotic plaques. Vascular smooth muscle cells, macrophages, or endothelial cells treated in vitro with proatherogenic stimuli reveal certain features typical of autophagy, such as LC3 processing, formation of myelin figures, and extensive vacuolization. However, despite the increasing interest in autophagy, its role in atherosclerosis remains poorly understood. Most likely, autophagy safeguards plaque cells against cellular distress, in particular oxidative injury, by degrading the damaged intracellular material. In this way, autophagy is antiapoptotic and contributes to cellular recovery in an adverse environment. Because atherosclerosis is an inflammatory disorder of the arterial intima, pharmacologic approaches have recently been developed to stabilize vulnerable, rupture-prone lesions through selective induction of macrophage autophagic death.

Autophagy plays a protective role in free cholesterol overload-induced death of smooth muscle cells

“…Accumulation of FC can be observed in foam-cell like macrophages or SMCs in advanced plaques, but these cells usually do not undergo apoptotic cell death. Similar to our fi nding, activation of autophagy in SMCs was also reported in several other in vitro experiments ( 23 ). Exposure to the products of lipid peroxidation, such as 4-hydroxynonenal (4-HNE), activated autophagy in cultured rat aortic SMCs, and inhibition of autophagy by 3-MA caused 4-HNE-induced cell death ( 24 ).…”

XBP1 mRNA Splicing Triggers an Autophagic Response in Endothelial Cells through BECLIN-1 Transcriptional Activation

“…Diseases such as atherosclerosis show evidence of cellular senescence characterized by reduced cell proliferation, irreversible growth arrest, and apoptosis. Nonetheless, a growing body of evidence suggests that elucidation of the signaling pathways regulating autophagy may provide novel therapeutic approaches in the prevention or treatment of atherosclerosis (1). Recent studies have reported that autophagy becomes dysfunctional in atherosclerosis, and its deficiency promotes atherosclerosis in part through inflammasome hyperactivation (2).…”

Cathepsin L stimulates autophagy and inhibits apoptosis of ox-LDL-induced endothelial cells: Potential role in atherosclerosis

“…Autophagy is a catabolic pathway for the bulk turnover of long-lived proteins and organelles via lysosomal degradation. Basal autophagy is a survival mechanism safeguarding vascular cells against oxidative injury, metabolic stress and inflammation (9,10); it is protective against EC injury and was observed in atherosclerotic plaques (11)(12)(13)(14)(15). Degradation of autophagolysosomal content is impaired in CATL(-/-) mice (16).…”