The role of autophagy in abdominal aortic aneurysm: protective but dysfunctional

Figures & data

Figure 1. Potential molecular mechanism by which autophagy plays a protective role in AAA pathogenesis. Thrombosis: Enhanced autophagy could decrease intraluminal thrombosis by reducing the aggregation of platelets. Macrophages: Autophagy deficiency leads to hyperactivation of the macrophage inflammasome and enhances plaque progression, thereby releasing inflammatory cytokines, such as TNF-α, IL-1β, and MMP-2, which ultimately exacerbate AAA formation. VSMC senescence: Deficient autophagy could accumulate SQSTM1/p62 and accelerate the development of stress-induced senescence, as indicated by cellular and nuclear hypertrophy, CDKN2A-RB-mediated G1 phase arrest and senescence-associated β-galactosidase activity. Atherosclerosis: Deficient autophagy exacerbates atherosclerotic plaques by reducing cholesterol efflux and exacerbating VSMC-derived foam cell generation

Table 1. Pharmacological treatment of AAA via autophagy

Drugs	Types	Target	Model	Main findings	Ref
rapamycin	Autophagy Inducer	mTOR signaling	intraluminal elastase perfusion C57BL/6 J mice	reduces the aortic aneurysm expansion	^[Citation26]
wortmannin	Autophagy Inducer/inhibitor	PI3K/AKT	Sprague-Dawley rats(PPE)	1.reduces the aortic diameter; 2.decreases Elastin destruction score and SMC destruction score	^[Citation94]
calorie restriction	Autophagy Inducer	SIRT1	angiotensin II (AngII)–induced Apoe −/− mice	1.reduced the incidence of AAA formation; attenuated 2.aortic elastin degradation	^[Citation87]
metformin	Autophagy inducer	PI3K/AKT/mTOR	angiotensin II (AngII)–induced Apoe −/− mice	attenuates the formation and the diameter	^[Citation86]
γ δT cells	/	PI3K/AKT	C57BL/6 mice (PPE)	reduces the aortic diameter	^[Citation95]
Curcumin	Autophagy inducer	EP300	angiotensin II (AngII)–induced Apoe −/− mice		^[Citation96]

Table 2. Autophagy-related MicroRNA in AAA

RNA	Type	Pathway	Tissue specimen	Main findings	Ref
MicroRNA‑26a	Inducing autophagy	PTEN/AKT/mTOR	H 2 O 2 -induced injured VSMC	Attenuates VSMC injury	^[Citation97]
MicroRNA −33-5p	Inducing autophagy	PI3K/Akt	THP-1 human macrophage cell	suppresses AAA progression	^[Citation98]
MicroRNA −195	Inducing autophagy	VEGF/PI3K/Akt	angiotensin II‑vascular smooth muscle cells	suppresses the protein expression of VEGF, PI3K and p‑Akt	^[Citation99]

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