title: miRNA-145 inhibits VSMC proliferation by targeting CD40.
abstract: Recent studies have demonstrated functions of miR-145 in vascular smooth muscle cells (VSMCs) phenotypes and vascular diseases. In this study, we aim to determine whether CD40 is involved in miR-145 mediated switch of VSMC phenotypes. In cultured VSMCs, the effects of miR-145 and CD40 on TNF-α, TGF-β, and Homocysteine (Hcy) induced cell proliferation were evaluated by over-expression of miR-145 or by siRNA-mediated knockdown of CD40. We also used ultrasound imaging to explore the effect of miR-145 on carotid artery intima-media thickness (CIMT) in atherosclerotic cerebral infarction (ACI) patients. The results showed 50 ng/mL TNF-α, 5 ng/mL TGF-β, and 500 μmol/L Hcy significantly increased the expression of CD40, both at mRNA and protein levels, and also induced the proliferation of VSMCs. We found that over-expression of miR-145 significantly inhibited the expression of CD40 and the differentiation of VSMCs, and over-expression of miR-145 decreased IL-6 levels in VSMC supernatants. In ACI patients, the lower expression of miR-145 was associated with thicker CIMT and higher levels of plasma IL-6. Our results suggest that the miR-145/CD40 pathway is involved in regulating VSMC phenotypes in TNF-α, TGF-β, and Hcy induced VSMCs proliferation model. Targeting miR-145/CD40 might be a useful strategy for treating atherosclerosis.
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Bikui
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Guo