The Role of Autophagy in the Pathogenesis of Atherosclerosis

Shin Kyoung Hur; Seung Hee Park; Goo Taeg Oh

doi:10.12997/jla.2016.5.1.1

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Hur, Park, and Oh: The Role of Autophagy in the Pathogenesis of Atherosclerosis

Review

Journal of Lipid and Atherosclerosis 2016; 5(1): 1-10.

Published online: 30 June 2016

DOI: https://doi.org/10.12997/jla.2016.5.1.1

The Role of Autophagy in the Pathogenesis of Atherosclerosis

Shin Kyoung Hur, Seung Hee Park, Goo Taeg Oh

Department of Life Sciences, Ewha Womans University, Seoul, Korea.

Corresponding Author: Goo Taeg Oh, Department of Life Sciences, Ewha Womans University, 52, Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Korea. Tel: +82-2-3277-4128, 4253, Fax: +82-2-3277-3760, gootaeg@ewha.ac.kr

Received 13 June 2016 Revised 22 June 2016 Accepted 23 June 2016

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Autophagy, Atherosclerosis, Vascular disease

Figures and Tables

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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