Tanshinone ⅡA inhibits VSMC inflammation and proliferation in vivo and in vitro by downregulating miR-712-5p expression.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 1254354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0712 (Electronic) Linking ISSN: 00142999 NLM ISO Abbreviation: Eur J Pharmacol Subsets: MEDLINE
    • Publication Information:
      Publication: 2005- : Amsterdam : Elsevier Science
      Original Publication: Amsterdam, North Holland Pub. Co.
    • Subject Terms:
      MicroRNAs*; Abietanes/*pharmacology ; Anti-Inflammatory Agents/*pharmacology ; Myocytes, Smooth Muscle/*drug effects; Animals ; Carotid Arteries/pathology ; Cell Line ; Cell Proliferation/drug effects ; Cytokines/genetics ; Cytokines/metabolism ; Down-Regulation/drug effects ; Hyperplasia/genetics ; Hyperplasia/metabolism ; Hyperplasia/pathology ; Kruppel-Like Factor 4 ; Kruppel-Like Transcription Factors/genetics ; Male ; Mice, Inbred C57BL ; Muscle, Smooth, Vascular/cytology ; Myocytes, Smooth Muscle/metabolism ; Neointima/genetics ; Neointima/metabolism ; Neointima/pathology
    • Abstract:
      The inflammation and proliferation of vascular smooth muscle cells (VSMCs) are the basic pathological feature of proliferative vascular diseases. Tanshinone ⅡA (Tan ⅡA), which is the most abundant fat-soluble element extracted from Salvia miltiorrhiza, has potent protective effects on the cardiovascular system. However, the underlying mechanism is still not fully understood. Here, we show that Tan ⅡA significantly inhibits neointimal formation and decreases VSMC inflammation by upregulating the expression of KLF4 and inhibiting the activation of NFκB signaling. Using a microRNA array analysis, we found that miR-712-5p expression is significantly upregulated in tumor necrosis factor alpha (TNF-α)-treated VSMCs. Loss- and gain-of-function experiments revealed that transfection of miR-712-5p mimic promotes, whereas depletion of miR-712-5p suppresses TNF-α-induced VSMC inflammation, leading to amelioration of intimal hyperplasia induced by carotid artery ligation. Moreover, depletion of miR-712-5p by its antagomir largely abrogates TNF-α-induced VSMC proliferation. Our findings suggest that miR-712-5p mediates the stimulatory effect of TNF-α on VSMC inflammation, and that Tan ⅡA inhibits VSMC inflammation and proliferation in vivo and in vitro by suppression of miR-712-5p expression. Targeting miR-712-5p may be a novel therapeutic strategy to prevent proliferative vascular diseases.
      (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Inflammation; Proliferation; Tanshinone ⅡA; VSMCs; miR-712-5p
    • Accession Number:
      0 (Abietanes)
      0 (Anti-Inflammatory Agents)
      0 (Cytokines)
      0 (Klf4 protein, mouse)
      0 (Kruppel-Like Factor 4)
      0 (Kruppel-Like Transcription Factors)
      0 (MIRN712 microRNA, mouse)
      0 (MicroRNAs)
      03UUH3J385 (tanshinone)
    • Publication Date:
      Date Created: 20200511 Date Completed: 20210324 Latest Revision: 20211204
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.ejphar.2020.173140
    • Accession Number:
      32387370