Protective Effect of Hydrogen Sulfide on Balloon Injury-Induced Neointima Hyperplasia in Rat Carotid Arteries

摘要

Endogenous hydrogen sulfide (H2S), generated from homocysteine metabolism mainly catalyzed by cystathionine γ-lyase (CSE), possesses important functions in the cardiovascular system. In this study, we investigated the role of H2S during the pathogenesis of neointimal formation induced by balloon injury in rats. CSE mRNA levels were reduced by 86.5% at 1 week and 64.0% at 4 weeks after balloon injury compared with the uninjured controls. CSE activity was also correspondingly reduced. Endogenous production of H2S in the injured carotid artery was significantly inhibited at 1 week and 4 weeks after balloon injury. Treatment with NaHS (a donor of H2S) enhanced methacholine-induced vasorelaxation of balloon-injured artery. More importantly, treatment with NaHS significantly inhibited neointima formation (0.15 ± 0.01 mm² versus 0.21 ± 0.01 mm², >P < 0.001) of the balloon-injured carotid arteries and reduced the intima/media ratio (1.05 ± 0.07 versus 1.43 ± 0.06, >P < 0.001). A significant decrease in vascular smooth muscle cell proliferation was demonstrated by bromodeoxyuridine incorporation at day 7 after injury. In conclusion, CSE expression and H2S production are reduced during the development of balloon injury-induced neointimal hyperplasia, and treatment with NaHS significantly reduces neointimal lesion formation.