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Review
. 2022 Mar 16;118(4):934-950.
doi: 10.1093/cvr/cvab158.

The role of autophagy in cardiovascular pathology

Damián Gatica  1 , Mario Chiong  2 , Sergio Lavandero  2   3   4 , Daniel J Klionsky  1
Affiliations
Review

The role of autophagy in cardiovascular pathology

Damián Gatica et al. Cardiovasc Res. .

Abstract

Macroautophagy/autophagy is a conserved catabolic recycling pathway in which cytoplasmic components are sequestered, degraded, and recycled to survive various stress conditions. Autophagy dysregulation has been observed and linked with the development and progression of several pathologies, including cardiovascular diseases, the leading cause of death in the developed world. In this review, we aim to provide a broad understanding of the different molecular factors that govern autophagy regulation and how these mechanisms are involved in the development of specific cardiovascular pathologies, including ischemic and reperfusion injury, myocardial infarction, cardiac hypertrophy, cardiac remodelling, and heart failure.

Keywords: Autophagosome; Cardiomyocyte; Heart; Lysosome; Vascular.

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Figures

Figure 1
Figure 1
During macroautophagy different cytoplasmic components are enclosed by the expanding phagophore. Maturation of the phagophore results in the sequestration of the cargo inside double-membrane autophagosomes. Fusion between autophagosomes and lysosomes results in the formation of an autolysosome, where the sequestered cargo is degraded by lysosomal hydrolases. Macromolecules obtained from cargo degradation are transported back into the cytosol to be reutilized.
Figure 2
Figure 2
The proposed structure of the PtdIns3K complex I (top) and PtdIns3K complex II (bottom). Note that not all PtdIns3K complex I and complex II factors, including RUBCN and SH3GLB1, are shown.
Figure 3
Figure 3
Translocation of the ULK complex to the ER leads to the phosphorylation and activation of the PtdIns3K complex I, which generates PtdIns3P-rich ER subdomains known as omegasomes. ZFYVE1, WDR45/WIPI4, and WIPI2B are recruited to omegasomes by binding PtdIns3P. WIPI4 binds ATG2A, which tethers the ER to the growing phagophore and transports lipids from one side to the other. ATG9A binds ATG2A, and the former moves lipids from one side of the membrane leaflet to the other, expanding the phagophore. WIPI2B recruits the ATG12–ATG5-ATG16L1 complex, inducing the lipidation of LC3 at the phagophore. Different sources provide membranes for phagophore expansion.
Figure 4
Figure 4
The ubiquitin-like proteins ATG12 and the LC3/GABARAP family go through activation by ATG7 and conjugation by ATG10 and ATG3, respectively. Covalent binding between ATG12–ATG5 leads to forming a dimeric ATG12–ATG5-ATG16L1 complex, which is recruited to the phagophore by WIPI2B, promoting the ligation of LC3 to PE. LC3-II/LC3–PE can be deconjugated by ATG4, the same protein involved in LC3 initial processing. GTAMAV, C-terminal amino acid residues; PE, phosphatidylethanolamine.
Figure 5
Figure 5
Role of autophagy in the development of vascular diseases using in vivo models and VSMC phenotypic change using in vitro models. AGES, advanced glycation end products; Ang II, angiotensin II; Hhc, hyperhomocysteinemia; PDGF-BB, platelet-derived growth factor-BB; TNF, tumor necrosis factor; VSMC, vascular smooth muscle cell.
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References

    1. Lahiri V, Hawkins WD, Klionsky DJ.. Watch what you (self-) eat: autophagic mechanisms that modulate metabolism. Cell Metab 2019;29:803–826. - PMC - PubMed
    1. Mazure NM, Pouyssegur J.. Hypoxia-induced autophagy: cell death or cell survival? Curr Opin Cell Biol 2010;22:177–180. - PubMed
    1. Smith MD, Harley ME, Kemp AJ, Wills J, Lee M, Arends M, von Kriegsheim A, Behrends C, Wilkinson S.. CCPG1 is a non-canonical autophagy cargo receptor essential for ER-phagy and pancreatic ER proteostasis. Dev Cell 2018;44:217–232.e211. - PMC - PubMed
    1. Fumagalli F, Noack J, Bergmann TJ, Cebollero E, Pisoni GB, Fasana E, Fregno I, Galli C, Loi M, Solda T, D'Antuono R, Raimondi A, Jung M, Melnyk A, Schorr S, Schreiber A, Simonelli L, Varani L, Wilson-Zbinden C, Zerbe O, Hofmann K, Peter M, Quadroni M, Zimmermann R, Molinari M.. Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery. Nat Cell Biol 2016;18:1173–1184. - PubMed
    1. Cuervo AM, , Wong E.. Chaperone-mediated autophagy: roles in disease and aging. Cell Res 2014;24:92–104. - PMC - PubMed

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