title: 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 gamma-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.
authors: Department of Pathology and Laboratory Medicine, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK, Canada S7N 0W8. qing.meng@usask.ca
authors: Qing H
authors: QH
authors: Meng
authors: Guangdong
authors: G
authors: Yang
authors: Wei
authors: W
authors: Yang
authors: Bo
authors: B
authors: Jiang
authors: Lingyun
authors: L
authors: Wu
authors: Rui
authors: R
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020212:Carotid Artery Injuries / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D002404:Catheterization / Q000009:adverse effects*; D049109:Cell Proliferation / Q000187:drug effects; D003542:Cystathionine gamma-Lyase / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D006965:Hyperplasia; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents
chemical_list: D012333:RNA, Messenger; D013440:Sulfides; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D006862:Hydrogen Sulfide