p62/mTOR/LXRα pathway inhibits cholesterol efflux mediated by ABCA1 and ABCG1 during autophagy blockage

Liang, Xiaofei; Wang, Chao; Sun, Yan; Song, Wei; Jiang, Lin; Li, Jiashan; Guan, Xue

doi:10.1016/j.bbrc.2019.04.134

Cited by 21 publications

(11 citation statements)

References 29 publications

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“…Further studies have shown that the blockage of autophagy could lead to lipid accumulation to promote the release of in ammatory factors. First, autophagy of the THP-1-derived macrophages is inhibited by ox-LDL in a concentration-dependent manner [33,34]. Owing the inhibition of autophagy, the autophagosomes and lysosomes cannot be fused, and thereby autophagy is blocked.…”

Section: Mir-30a-5p Overexpression Aggravates Macrophage Apoptosismentioning

confidence: 99%

MicroRNA-30a-5p-Mediated Autophagy Regulates Formation of Foam Cells from THP-1-derived Macrophages

Geng¹,

Wang²,

Su³

et al. 2021

Preprint

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MicroRNAs are widely considered to be involved in the pathogenesis of atherosclerosis. Whereas the importance of miR-30a-5p as a tumor growth-promoting factor has been extensively studied, the relationship between this particular microRNA and atherosclerosis remains to be clarified. In this study, the role of miR-30a-5p in the formation of foam cells from THP-1-derived macrophages was investigated. It was found that miR-30a-5p could robustly regulate the pathological process of atherosclerosis by inhibiting autophagy and increasing the accumulation of lipids, the expression of inflammatory factors, and the apoptosis of macrophages. These results provide guidance for future assessments of the progression of atherosclerosis and for the development of intervention targets for the treatment of this disease.

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Section: Mir-30a-5p Overexpression Aggravates Macrophage Apoptosismentioning

confidence: 99%

MicroRNA-30a-5p-Mediated Autophagy Regulates Formation of Foam Cells from THP-1-derived Macrophages

Geng¹,

Wang²,

Su³

et al. 2021

Preprint

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“…Primary cultured THP-1 cells were plated in 6/12/24-well plates with PMA for 48 h. After this period, cells were induced into macrophages. And foam cell model was established by incubation of cells with excess oxidized low-density lipoprotein (ox-LDL) for 48 h. Our previous research indicated that ox-LDL at a final concentration of 50 μg/ml can induce foam cell formation [11].…”

Section: Construction Of Foam Cell Modelmentioning

confidence: 99%

“…Several studies have emphasized the role of autophagy in the pathological process of AS, especially macrophage autophagy [9,10]. Our previous research also showed that the upregulation of autophagy in macrophages can promote intracellular cholesterol efflux and reduce foam cell formation through p62/mTOR/LXRa pathway [11]. Zhou's study indicated that defected autophagic flux remarkably increased the expression of matrix metalloproteinase 9 (MMP9) [12].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-761 modulates foam cell formation and inflammation through autophagy in the progression of atherosclerosis

et al. 2020

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Macrophage-derived foam cells formation is the initial stage of atherosclerosis, and lipid-laden macrophage accumulation is also considered as the symbol of unstable plaque. Autophagy is a subcellular process responsible for the degradation of damaged organelles and aggregated proteins in cells (Grootaert in Oxid Med Cell Longev: 7687083, 2018). Macrophage autophagy plays an important role in atherosclerosis under various stress conditions, and microRNAs are involved in this complicated process. The present study was programmed to explore the effects of microRNA-761 on macrophage-derived foam cell formation, focusing on the role of autophagy in this pathological process. The differentiated human THP-1 macrophages were used in the study. THP-1-derived macrophages were treated with miR-761 mimics or inhibitors and cultured with oxidized low-density lipoprotein to mimic the lipid-rich environment in blood vessel. The expression of miR-761 and mRNA levels of IL-1β and IL-18 were analyzed by quantitative real-time PCR. The effect of miR-761 on autophagy was evaluated by the protein levels of Beclin1, p62/SQSTM1, microtubule-associated protein light chain 3, mammalian target of rapamycin (mTOR), and unc-51-like autophagy activating kinase 1 (ULK1), determined by immunoblot and autophagic flux detected by fluorescent staining. The secretion of IL-1β and IL-18 was tested by enzyme-linked immunosorbent reaction kit. Lipid accumulation in foam cells was detected by oil red "O" staining. We demonstrated that miR-761 was able to repress foam cell formation and reduce the production of atherogenic inflammatory cytokines IL-1β and IL-18 in an autophagy-dependent manner in atherosclerosis, possibly via mTOR-ULK1 signaling pathway. In summary, we described an athero-protective function of miR-761 in macrophages incubated with excess ox-LDL and identified an important novel modulator of mTOR signaling and autophagy in macrophage-derived foam cells. This finding may provide a potential target for the prevention and early treatment in high-risk group of atherosclerosis.

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“…These lipid-loaded cells also intensify arterial wall inflammation, thus resulting in multiple fatal pathological consequences, such as rupture, hemorrhage, and calcification (Lu and Daugherty, 2015). Macrophages phagocytose cholesterol lipid droplets and also trigger cholesterol efflux, thereby reducing lipid accumulation in foam cells and delaying AS progression (Liang et al, 2019). ABCA1 presents itself as the major protein on the membrane of adipocytes, which transports cellular cholesterol and phospholipids to extracellular apoA-I by assembly of high-density lipoprotein (HDL), thereby maintaining cholesterol homeostasis (Tian et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Curcumin promotes cholesterol efflux by regulating ABCA1 expression through miR-125a-5p/SIRT6 axis in THP-1 macrophage to prevent atherosclerosis

Tan

Zhou

Wen³

et al. 2021

J. Toxicol. Sci.

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p62/mTOR/LXRα pathway inhibits cholesterol efflux mediated by ABCA1 and ABCG1 during autophagy blockage

Cited by 21 publications

References 29 publications

MicroRNA-30a-5p-Mediated Autophagy Regulates Formation of Foam Cells from THP-1-derived Macrophages

MicroRNA-30a-5p-Mediated Autophagy Regulates Formation of Foam Cells from THP-1-derived Macrophages

MicroRNA-761 modulates foam cell formation and inflammation through autophagy in the progression of atherosclerosis

Curcumin promotes cholesterol efflux by regulating ABCA1 expression through miR-125a-5p/SIRT6 axis in THP-1 macrophage to prevent atherosclerosis

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