J Lipid Atheroscler.  2016 Jun;5(1):1-10. 10.12997/jla.2016.5.1.1.

The Role of Autophagy in the Pathogenesis of Atherosclerosis

• Hur SK
• Park SH
• Oh GT

• KMID: 2328833
• DOI: http://doi.org/10.12997/jla.2016.5.1.1

Abstract

Autophagy is a life-sustaining process by which cytoplasmic constituents are segregated in double-lipid bilayer membrane vesicles and undergo degradation into lysosomes. In recent studies, the basal autophagy is an indispensable process mediating proper vascular function in the body. Moreover, autophagy activated by many stress-related stimuli in the arterial wall protects endothelial cells and smooth muscle cells against cell death and the progression of vascular disease including atherosclerosis. Autophagy is protective to atherosclerosis during early stage but becomes dysfunctional in advanced atherosclerotic lesions. Following this finding, the need is emphasized which pharmacological development with compounds that activate the protective effects of autophagy in the vascular disease. Autophagy stimulated by oral or vascular delivery of rapamycin or derivatives effectively suppressed the atherosclerotic plaque growth and plaque destabilization. In this review, the recent finding is summarized on the role of autophagy in atherosclerosis and find out whether the activation or rescue of autophagy could provide a breakthrough in the treatment of atherosclerosis.

Keyword

Autophagy; Atherosclerosis; Vascular disease

MeSH Terms

Atherosclerosis*
Autophagy*
Cell Death
Cytoplasm
Endothelial Cells
Lysosomes
Membranes
Myocytes, Smooth Muscle
Negotiating
Plaque, Atherosclerotic
Sirolimus
Vascular Diseases
Sirolimus

Figure

• 

  Fig. 1 The different types of autophagy. (A) Aggrephagy, (B) Mitophagy, (C) Lipophagy, (D) Xenophagy, (E) Schematic overview of the autophagic pathway.

• 

  Fig. 2 Potential role of autophagy in atherosclerosis. (A) Oxidative stress induced by the production of reactive oxygen species or the oxidized lipids is abundant in advanced atherosclerotic plaques. In the case of mild oxidative stress, activated autophagy promotes the removal of damaged organelles (eg, depolarized mitochondria) and contributes to cellular recovery, (B) Severe oxidative stress makes excessive cellular damage. Autophagy is not sufficient for the removal of that. Depolarized mitochondria release apoptosis inducer such as cytochrome c. Lysosome membrane damage results in cytosolic leakage of hydrolases, which could cause substantial cytosolic damage followed by apoptosis. Moreover, formation of ceroid that cannot be degraded by lysosomal hydrolases lead to preferential allocation of lysosomal enzymes to ceroid-loaded lysosomes at the expense of active autolysosomes which, in turn, would lead to the autophagy inhibition followed by apoptosis.

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