title: Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury.
abstract: Carbon monoxide (CO), one of the products of heme oxygenase action on heme, prevents arteriosclerotic lesions that occur following aorta transplantation; pre-exposure to 250 parts per million of CO for 1 hour before injury suppresses stenosis after carotid balloon injury in rats as well as in mice. The protective effect of CO is associated with a profound inhibition of graft leukocyte infiltration/activation as well as with inhibition of smooth muscle cell proliferation. The anti-proliferative effect of CO in vitro requires the activation of guanylate cyclase, the generation of cGMP, the activation of p38 mitogen-activated protein kinases and the expression of the cell cycle inhibitor p21Cip1. These findings demonstrate a protective role for CO in vascular injury and support its use as a therapeutic agent.
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Montefiore University Hospital, Pittsburgh, Pennsylvania, USA.
authors.forename: Leo E
authors.initials: LE
authors.lastname: Otterbein
authors.forename: Brian S
authors.initials: BS
authors.lastname: Zuckerbraun
authors.forename: Manabu
authors.initials: M
authors.lastname: Haga
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Ruiping
authors.initials: R
authors.lastname: Song
authors.forename: Anny
authors.initials: A
authors.lastname: Usheva
authors.forename: Christina
authors.initials: C
authors.lastname: Stachulak
authors.forename: Natalya
authors.initials: N
authors.lastname: Bodyak
authors.forename: R Neal
authors.initials: RN
authors.lastname: Smith
authors.forename: Eva
authors.initials: E
authors.lastname: Csizmadia
authors.forename: Shivraj
authors.initials: S
authors.lastname: Tyagi
authors.forename: Yorihiro
authors.initials: Y
authors.lastname: Akamatsu
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Flavell
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.forename: Edith
authors.initials: E
authors.lastname: Tzeng
authors.forename: Fritz H
authors.initials: FH
authors.lastname: Bach
authors.forename: Augustine M K
authors.initials: AM
authors.lastname: Choi
authors.forename: Miguel P
authors.initials: MP
authors.lastname: Soares
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control*; D002248:Carbon Monoxide / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004789:Enzyme Activation; D006084:Graft Rejection / Q000517:prevention & control*; D006162:Guanylate Cyclase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: C493957:Cdkn1a protein, mouse; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D006162:Guanylate Cyclase; D006152:Cyclic GMP