Open Access

Metformin inhibits cholesterol‑induced adhesion molecule expression via activating the AMPK signaling pathway in vascular smooth muscle cells

  • Authors:
    • Qi Liu
    • Mengyue Yang
    • Lu Zhang
    • Ruoxi Zhang
    • Xingtao Huang
    • Xuedong Wang
    • Wenjuan Du
    • Jingbo Hou
  • View Affiliations

  • Published online on: August 9, 2021     https://doi.org/10.3892/mmr.2021.12348
  • Article Number: 709
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Recruitment of lymphocytes to the vascular wall contributes to the pathogenesis of atherosclerosis (AS). The expression of cellular adhesion molecules, such as vascular cell adhesion molecule‑1 and intercellular adhesion molecule‑1, serves a critical role in mediating lymphocyte adhesion to the vascular wall. Cholesterol loading induces the expression of adhesion molecules in vascular smooth muscle cells (VSMCs), but the underlying mechanism is not completely understood. The present study aimed to investigate the mechanism underlying the effects of cholesterol on adhesion molecule expression, and whether metformin protected VSMCs against cholesterol‑induced functional alterations. Human VSMCs were loaded with cholesterol and different concentrations of metformin. The expression levels of adhesion molecules were assessed via reverse transcription‑quantitative PCR and western blotting. Reactive oxygen species (ROS) accumulation and levels were quantified via fluorescence assays and spectrophotometry, respectively. AMP‑activated protein kinase (AMPK), p38 MAPK and NF‑κB signaling pathway‑related protein expression levels were evaluated via western blotting. Compared with the control group, cholesterol loading significantly upregulated adhesion molecule expression levels on VSMCs by increasing intracellular ROS levels and activating the p38 MAPK and NF‑κB signaling pathways. Metformin decreased cholesterol‑induced VSMC damage by activating the AMPK signaling pathway, and suppressing p38 MAPK and NF‑κB signaling. The present study indicated the therapeutic potential of metformin for VSMC protection, reduction of monocyte adhesion, and ultimately, the prevention and treatment of AS.
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October-2021
Volume 24 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Liu Q, Yang M, Zhang L, Zhang R, Huang X, Wang X, Du W and Hou J: Metformin inhibits cholesterol‑induced adhesion molecule expression via activating the AMPK signaling pathway in vascular smooth muscle cells. Mol Med Rep 24: 709, 2021
APA
Liu, Q., Yang, M., Zhang, L., Zhang, R., Huang, X., Wang, X. ... Hou, J. (2021). Metformin inhibits cholesterol‑induced adhesion molecule expression via activating the AMPK signaling pathway in vascular smooth muscle cells. Molecular Medicine Reports, 24, 709. https://doi.org/10.3892/mmr.2021.12348
MLA
Liu, Q., Yang, M., Zhang, L., Zhang, R., Huang, X., Wang, X., Du, W., Hou, J."Metformin inhibits cholesterol‑induced adhesion molecule expression via activating the AMPK signaling pathway in vascular smooth muscle cells". Molecular Medicine Reports 24.4 (2021): 709.
Chicago
Liu, Q., Yang, M., Zhang, L., Zhang, R., Huang, X., Wang, X., Du, W., Hou, J."Metformin inhibits cholesterol‑induced adhesion molecule expression via activating the AMPK signaling pathway in vascular smooth muscle cells". Molecular Medicine Reports 24, no. 4 (2021): 709. https://doi.org/10.3892/mmr.2021.12348