Protective Effect of Hydrogen Sulfide on Balloon Injury-Induced Neointima Hyperplasia in Rat Carotid Arteries
Abstract
Endogenous hydrogen sulfide (H 2 S), generated from homocysteine metabolism mainly catalyzed by cystathionine -lyase (CSE), possesses important functions in the cardiovascular system. In this study, we investigated the role of H 2 S 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 H 2 S in the injured carotid artery was significantly inhibited at 1 week and 4 weeks after balloon injury. Treatment with NaHS (a donor of H 2 S) enhanced methacholine-induced vasorelaxation of balloon-injured artery. More importantly, treatment with NaHS significantly inhibited neointima formation (0.15 ± 0.01 mm 2 versus 0.21 ± 0.01 mm 2 , 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 H 2 S production are reduced during the development of balloon injury-induced neointimal hyperplasia, and treatment with NaHS significantly reduces neointimal lesion formation.