FGF21 induces autophagy‐mediated cholesterol efflux to inhibit atherogenesis via RACK1 up‐regulation

Lin, Xiaolan; Guo, Dongmin; Liu, Mi‐Hua; Zuo, Wang; Hu, Hui‐Jun; Qiufen, Tan; Hu, Xuemei; Wei, Lin; Pan, Yu‐Chen; Lin, Jun; Zeng, Zhaolin

doi:10.1111/jcmm.15118

Cited by 36 publications

(20 citation statements)

References 44 publications

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“…Several studies have shown a protective role of FGF-21 against atherosclerosis via the regulation of different signalling pathways involved in inflammation, oxidative stress, cholesterol synthesis, and cell viability. In ApoE −/− mice, FGF-21 treatment was described to mitigate atherosclerosis through the inhibition of NLRP3, the inhibition of factor-associated suicide (FAS) signalling, the reduction of cholesterol accumulation through the promotion of autophagy and by suppressing hepatic cholesterol synthesis, increasing adiponectin production by adipocytes, and attenuating endoplasmic-reticulum-stress-induced apoptosis [ 329 , 330 , 331 , 332 , 333 ]. In rats with atherosclerosis, FGF-21 decreases inflammation by increasing the signalling of nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response elements (ARE) and by reducing the expression of NF-κB [ 334 , 335 ].…”

Section: Role Of Some Adipokines In Inflammatory Processes Associamentioning

confidence: 99%

Adipokines and Inflammation: Focus on Cardiovascular Diseases

Feijóo‐Bandín

Aragón-Herrera

Moraña-Fernández

et al. 2020

IJMS

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It is well established that adipose tissue, apart from its energy storage function, acts as an endocrine organ that produces and secretes a number of bioactive substances, including hormones commonly known as adipokines. Obesity is a major risk factor for the development of cardiovascular diseases, mainly due to a low grade of inflammation and the excessive fat accumulation produced in this state. The adipose tissue dysfunction in obesity leads to an aberrant release of adipokines, some of them with direct cardiovascular and inflammatory regulatory functions. Inflammation is a common link between obesity and cardiovascular diseases, so this review will summarise the role of the main adipokines implicated in the regulation of the inflammatory processes occurring under the scenario of cardiovascular diseases.

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Section: Role Of Some Adipokines In Inflammatory Processes Associamentioning

confidence: 99%

Adipokines and Inflammation: Focus on Cardiovascular Diseases

Feijóo‐Bandín

Aragón-Herrera

Moraña-Fernández

et al. 2020

IJMS

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“…There was evidence demonstrating that autophagy activities were capable of weakening the extent of atheroma plaques via promoting cholesterol efflux of macrophages and then prohibiting foam cell formation [ 15 , 50 , 51 ]. Besides, autophagy was reported to modulate the polarization conversion of macrophage phenotype [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Rosuvastatin exerts anti-atherosclerotic effects by improving macrophage-related foam cell formation and polarization conversion via mediating autophagic activities

et al. 2021

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Background Atherosclerosis is a chronic vascular disease posing a great threat to public health. We investigated whether rosuvastatin (RVS) enhanced autophagic activities to inhibit lipid accumulation and polarization conversion of macrophages and then attenuate atherosclerotic lesions. Methods All male Apolipoprotein E-deficient (ApoE−/−) mice were fed high-fat diet supplemented with RVS (10 mg/kg/day) or the same volume of normal saline gavage for 20 weeks. The burden of plaques in mice were determined by histopathological staining. Biochemical kits were used to examine the levels of lipid profiles and inflammatory cytokines. The potential mechanisms by which RVS mediated atherosclerosis were explored by western blot, real-time PCR assay, and immunofluorescence staining in mice and RAW264.7 macrophages. Results Our data showed that RVS treatment reduced plaque areas in the aorta inner surface and the aortic sinus of ApoE−/− mice with high-fat diet. RVS markedly improved lipid profiles and reduced contents of inflammatory cytokines in the circulation. Then, results of Western blot showed that RVS increased the ratio LC3II/I and level of Beclin 1 and decreased the expression of p62 in aortic tissues, which might be attributed to suppression of PI3K/Akt/mTOR pathway, hinting that autophagy cascades were activated by RVS. Moreover, RVS raised the contents of ABCA1, ABCG1, Arg-1, CD206 and reduced iNOS expression of arterial wall, indicating that RVS promoted cholesterol efflux and M2 macrophage polarization. Similarly, we observed that RVS decreased lipids contents and inflammatory factors expressions in RAW264.7 cells stimulated by ox-LDL, accompanied by levels elevation of ABCA1, ABCG1, Arg-1, CD206 and content reduction of iNOS. These anti-atherosclerotic effects of RVS were abolished by 3-methyladenine intervention. Moreover, RVS could reverse the impaired autophagy flux in macrophages insulted by chloroquine. We further found that PI3K inhibitor LY294002 enhanced and agonist 740 Y-P weakened the autophagy-promoting roles of RVS, respectively. Conclusions Our study indicated that RVS exhibits atheroprotective effects involving regulation lipid accumulation and polarization conversion by improving autophagy initiation and development via suppressing PI3K/Akt/mTOR axis and enhancing autophagic flux in macrophages.

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“…There was evidence demonstrating that autophagy activities were capable of weakening the extent of atheroma plaques via promoting cholesterol e ux of macrophages and then prohibiting foam cell formation [15,50,51]. Besides, autophagy was reported to modulate the polarization conversion of macrophage phenotype [52].…”

Section: Discussionmentioning

confidence: 99%

Rosuvastatin exerts anti-atherosclerotic effects by improving macrophage-related foam cell formation and polarization conversion via mediating autophagic activities

Zhang

Qin

Wan

et al. 2021

Preprint

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Background Atherosclerosis is a chronic vascular disease posing a great threat to public health. We investigated whether rosuvastatin (RVS) enhanced autophagic activities to inhibit lipid accumulation and polarization conversion of macrophages and then attenuate atherosclerotic lesions. Methods All male Apolipoprotein E-deficient (ApoE-/-) mice were fed high-fat diet supplemented with RVS (10mg/kg/day) or the same volume of normal saline gavage for 20 weeks. The burden of plaques in mice were determined by histopathological staining. Biochemical kits were used to examine the levels of lipid profiles and inflammatory cytokines. The potential mechanisms by which RVS mediated atherosclerosis were explored by western blot, real-time PCR assay, and immunofluorescence staining in mice and RAW264.7 macrophages.Results Our data showed that RVS treatment reduced plaque areas in the aorta inner surface and the aortic sinus of ApoE-/- mice with high-fat diet. RVS markedly improved lipid profiles and reduced contents of inflammatory cytokines in the circulation. Then, results of Western blot showed that RVS increased the ratio LC3II/I and level of Beclin 1 and decreased the expression of p62 in aortic tissues, which might be attributed to suppression of PI3K/Akt/mTOR pathway, hinting that autophagy cascades were activated by RVS. Moreover, RVS raised the contents of ABCA1, ABCG1, Arg-1, CD206 and reduced iNOS expression of arterial wall, indicating that RVS promoted cholesterol efflux and M2 macrophage polarization. Similarly, we observed that RVS decreased lipids contents and inflammatory factors expressions in RAW264.7 cells stimulated by ox-LDL, accompanied by levels elevation of ABCA1, ABCG1, Arg-1, CD206 and content reduction of iNOS. These anti-atherosclerotic effects of RVS were abolished by 3-methyladenine intervention. Moreover, RVS could reverse the impaired autophagy flux in macrophages insulted by chloroquine. We further found that PI3K inhibitor LY294002 enhanced and agonist 740 Y-P weakened the autophagy-promoting roles of RVS, respectively. Conclusions Our study indicated that RVS exhibits atheroprotective effects involving regulation lipid accumulation and polarization conversion by improving autophagy initiation and development via suppressing PI3K/Akt/mTOR axis and enhancing autophagic flux in macrophages.

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FGF21 induces autophagy‐mediated cholesterol efflux to inhibit atherogenesis via RACK1 up‐regulation

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 36 publications

References 44 publications

Adipokines and Inflammation: Focus on Cardiovascular Diseases

Adipokines and Inflammation: Focus on Cardiovascular Diseases

Rosuvastatin exerts anti-atherosclerotic effects by improving macrophage-related foam cell formation and polarization conversion via mediating autophagic activities

Rosuvastatin exerts anti-atherosclerotic effects by improving macrophage-related foam cell formation and polarization conversion via mediating autophagic activities

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