Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury.
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.
Otterbein
Leo E
LE
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Montefiore University Hospital, Pittsburgh, Pennsylvania, USA.
Zuckerbraun
Brian S
BS
Haga
Manabu
M
Liu
Fang
F
Song
Ruiping
R
Usheva
Anny
A
Stachulak
Christina
C
Bodyak
Natalya
N
Smith
R Neal
RN
Csizmadia
Eva
E
Tyagi
Shivraj
S
Akamatsu
Yorihiro
Y
Flavell
Richard J
RJ
Billiar
Timothy R
TR
Tzeng
Edith
E
Bach
Fritz H
FH
Choi
Augustine M K
AM
Soares
Miguel P
MP
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
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