Mangiferin Inhibits PDGF-BB-Induced Proliferation and Migration of Rat Vascular Smooth Muscle Cells and Alleviates Neointimal Formation in Mice through the AMPK/Drp1 Axis

Oxid Med Cell Longev. 2021 Dec 3:2021:3119953. doi: 10.1155/2021/3119953. eCollection 2021.

Abstract

Mangiferin is a naturally occurring xanthone C-glycoside that is widely found in various plants. Previous studies have reported that mangiferin inhibits tumor cell proliferation and migration. Excessive proliferation and migration of vascular smooth muscle cells (SMCs) is associated with neointimal hyperplasia in coronary arteries. However, the role and mechanism of mangiferin action in neointimal hyperplasia is still unknown. In this study, a mouse carotid artery ligation model was established, and primary rat smooth muscle cells were isolated and used for mechanistic assays. We found that mangiferin alleviated neointimal hyperplasia, inhibited proliferation and migration of SMCs, and promoted platelets derive growth factors-BB- (PDGF-BB-) induced contractile phenotype in SMCs. Moreover, mangiferin attenuated neointimal formation by inhibiting mitochondrial fission through the AMPK/Drp1 signaling pathway. These findings suggest that mangiferin has the potential to maintain vascular homeostasis and inhibit neointimal hyperplasia.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Becaplermin / pharmacology*
  • Carotid Arteries / pathology
  • Cell Dedifferentiation / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Dynamins / metabolism*
  • Hyperplasia / metabolism
  • Hyperplasia / pathology
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mitochondrial Dynamics / drug effects
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • Xanthones / pharmacology*

Substances

  • Proliferating Cell Nuclear Antigen
  • Reactive Oxygen Species
  • Xanthones
  • Becaplermin
  • mangiferin
  • AMP-Activated Protein Kinases
  • Matrix Metalloproteinase 2
  • Dnm1l protein, mouse
  • Dynamins