The slow releasing hydrogen sulfide donor GYY4137 reduces neointima formation upon FeCl3 injury of the carotid artery in mice

Clin Hemorheol Microcirc. 2020;75(4):409-417. doi: 10.3233/CH-190747.

Abstract

Introduction: Neointima formation is closely linked to vascular stenosis and occurs after endothelial damage. Hydrogen sulfide is an endogenous pleiotropic mediator with numerous positive effects on the cardio vascular system.

Objective: This study evaluates the effect of the slow releasing hydrogen sulfide donor GYY4137 (GYY) on neointimal formation in vivo.

Methods: The effect of GYY on neointimal formation in the carotid artery was studied in the FeCl3 injury model in GYY- or vehicle-treated mice. The carotid arteries were studied at days 7 and 21 after treatment by means of histology and immunohistochemistry for proliferating cell nuclear antigen (PCNA) and alpha smooth muscle actin (α-SMA).

Results: GYY treatment significantly reduced the maximal diameter and the area of the newly formed neointima on both days 7 and 21 when compared to vehicle treatment. GYY additionally reduced the number of PCNA- and α-SMA-positive cells within the neointima on day 21 after FeCl3 injury of the carotid artery.

Conclusions: Summarizing, single treatment with the slow releasing hydrogen sulfide donor GYY reduced the extent of the newly formed neointima by affecting the cellular proliferation at the site of vascular injury.

Keywords: Pleiotropic mediator; arterial stenosis; basic science; gaseous transmitter; vascular disease.

MeSH terms

  • Animals
  • Carotid Arteries / drug effects
  • Carotid Artery, Common / physiopathology*
  • Disease Models, Animal
  • Hydrogen Sulfide / pharmacology
  • Male
  • Mice
  • Morpholines / pharmacology
  • Morpholines / therapeutic use*
  • Neointima / drug therapy*
  • Neointima / pathology
  • Organothiophosphorus Compounds / pharmacology
  • Organothiophosphorus Compounds / therapeutic use*

Substances

  • GYY 4137
  • Morpholines
  • Organothiophosphorus Compounds
  • Hydrogen Sulfide