Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury

Leo E. Otterbein, Brian S. Zuckerbraun, Manabu Haga, Fang Liu, Ruiping Song, Anny Usheva, Christina Stachulak, Natalya Bodyak, R. Neal Smith, Eva Csizmadia, Shivraj Tyagi, Yorihiro Akamatsu, Richard J. Flavell, Timothy R. Billiar, Edith Tzeng, Fritz H. Bach*, Augustine M.K. Choi, Miguel P. Soares

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

457 Scopus citations

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 antiproliferative 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.

Original languageEnglish
Pages (from-to)183-190
Number of pages8
JournalNature Medicine
Volume9
Issue number2
DOIs
StatePublished - 1 Feb 2003
Externally publishedYes

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