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

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.

Novel ray of hope for diabetic wound healing: Hydrogen sulfide and its releasing agents

“…Studies have shown that H 2 S can regulate thrombosis by interfering with platelet activation, H 2 S at physiological concentration may hinder the clustering of platelets caused by moderate stimulation, which may be attributed to the persulfuration of platelet-associated proteins and the antioxidant activity of H 2 S [45] , [46] , [47] , [48] . Moreover, GYY4137 acts as a slow-releasing H 2 S donor which was found to regulate and enhance endogenous thrombolysis by diminishing platelet aggregation and disrupting platelet activation and adhesion molecule-mediated aggregation [49] , [50] . Aged garlic extract slowly releases H 2 S to achieve physiological effects, which can inhibit platelet aggregation by inhibiting cAMP phosphodiesterase activity to increase cAMP levels [51] .…”