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

• DOI: 10.1186/s12967-021-02727-3
• Publication Date: 2021-02-11T08:04:45Z
• Authors: Xinxin Zhang; Yating Qin; Xiaoning Wan; Hao Liu; Chao Lv; Weibin Ruan; Lin He; Li Lu; Xiaomei Guo
• Keywords: Foam cell; Macrophage polarization

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