Suramin inhibits phenotypic transformation of vascular smooth muscle cells and neointima hyperplasia by suppressing transforming growth factor beta receptor 1 /Smad2/3 pathway activation

Eur J Pharmacol. 2024 Apr 5:968:176422. doi: 10.1016/j.ejphar.2024.176422. Epub 2024 Feb 15.

Abstract

Vascular smooth muscle cells (VSMCs) contribute to neointimal hyperplasia (NIH) after vascular injury, a common feature of vascular remodelling disorders. Suramin is known to exert antitumour effects by inhibiting the proliferation of various tumour cells; however, its effects and mechanism on VSMCs remain unclear. This study investigated the effects of suramin on human aortic smooth muscle cells (HASMCs), rat aortic smooth muscle cells (RASMCs) and NIH to examine its suitability for the prevention of vascular remodelling disorders. In vitro, suramin administration reduced platelet-derived growth factor type BB (PDGF-BB)-stimulated proliferation, migration, and dedifferentiation of VSMCs through a transforming growth factor beta receptor 1 (TGFBR1)/Smad2/3-dependent pathway. Suramin dramatically inhibited NIH ligation in the left common carotid artery (LCCA) vivo. Therefore, our results indicate that suramin protects against the development of pathological vascular remodelling by attenuating VSMCs proliferation, migration, and phenotypic transformation and may be used as a potential medicine for the treatment of NIH.

Keywords: Neointima hyperplasia; Phenotypic transformation; Suramin; Transforming growth factor beta receptor 1; Vascular smooth muscle cells.

MeSH terms

  • Animals
  • Becaplermin / pharmacology
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Humans
  • Hyperplasia / pathology
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle
  • Neointima* / pathology
  • Rats
  • Receptor, Transforming Growth Factor-beta Type I / metabolism
  • Suramin* / metabolism
  • Suramin* / pharmacology
  • Vascular Remodeling

Substances

  • Suramin
  • Receptor, Transforming Growth Factor-beta Type I
  • Becaplermin