title: miR-145 mediated the role of aspirin in resisting VSMCs proliferation and anti-inflammation through CD40.
abstract: Aspirin (ASA) is the most widely used medicine to prevent cardiovascular diseases; however, the mechanisms by which ASA exerts its anti-proliferative effect remain not fully understood. This study was designed to investigate whether miR-145 is involved in the regulation of vascular smooth muscle cells' (VSMCs) proliferation and to determine the anti-inflammatory effects of ASA via its regulation of CD40 to provide a new theoretical basis for the pharmacological effect of aspirin.
  
  
  
  The TNF-α induced proliferation model of VSMCs was divided into different groups with or without aspirin. Cell proliferation was detected by EdU; Real-time PCR was used to detect the mRNA expression of miR-145, CD40, and Calponin, a VSMCs differentiation marker gene. Western blot was used to detect the protein expression of CD40; ELISA was used to determine the concentrations of the inflammatory cytokine IL-6 in cell supernatants.
  
  
  
  The proliferation of VSMCs was stimulated by TNF-α and accompanied by decreased levels of Calponin. TNF-α also decreased the levels of miR-145 and increased the levels of CD40 and IL-6. Pretreatment with 20 μg/mL of aspirin in VSMCs could partially block the above-mentioned effects induced by TNF-α. The protective effects of ASA in VSMCs were reversed by a pretreatment with a miR-145 inhibitor. We also found that the expression of miR-145 in peripheral blood mononuclear cells in ischemic stroke patients was significantly increased after a 10-day treatment with aspirin.
  
  
  
  miR-145 is involved in the anti-proliferation and anti-inflammation effects of aspirin on VSMCs by inhibiting the expression of CD40.
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
authors.forename: Lijin
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China. grfw2012@aliyun.com.
authors.forename: Ren
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Bikui
authors.initials: B
authors.lastname: Zhang
mesh_terms: D001241:Aspirin / Q000494:pharmacology*; D050197:Atherosclerosis / Q000150:complications / Q000235:genetics; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics; D019013:CD40 Antigens / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics* / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020521:Stroke / Q000150:complications / Q000235:genetics; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D019013:CD40 Antigens; D015850:Interleukin-6; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D001241:Aspirin
keywords: Aspirin; CD40; Proliferation; VSMCs; miR-145