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- Title
Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury.
- Authors
Otterbein, Leo E; Zuckerbraun, Brian S; Haga, Manabu; Liu, Fang; Song, Ruiping; Usheva, Anny; Stachulak, Christina; Bodyak, Natalya; Smith, R Neal; Csizmadia, Eva; Tyagi, Shivraj; Akamatsu, Yorihiro; Flavell, Richard J; Billiar, Timothy R; Tzeng, Edith; Bach, Fritz H; Choi, Augustine M K; Soares, Miguel P
- 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.
- Publication
Nature medicine, 2003, Vol 9, Issue 2, p183
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/nm817