1. Academic Validation
  2. 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

  • J Transl Med. 2021 Feb 10;19(1):62. doi: 10.1186/s12967-021-02727-3.
Xinxin Zhang 1 Yating Qin 1 Xiaoning Wan 1 Hao Liu 1 Chao Lv 1 Weibin Ruan 1 Lin He 2 3 Li Lu 4 5 Xiaomei Guo 6
Affiliations

Affiliations

  • 1 Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 2 Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. [email protected].
  • 3 Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiaotong University, Shanghai, China. [email protected].
  • 4 Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. [email protected].
  • 5 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. [email protected].
  • 6 Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. [email protected].
Abstract

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.

Keywords

Atherosclerosis; Autophagy; Lipid accumulation; Macrophage polarization; Rosuvastatin.

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