Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury.
Cyclin-Dependent Kinase Inhibitor p21
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases
Nitric Oxide Synthase
p38 Mitogen-Activated Protein Kinases
Angioplasty, Balloon, Coronary
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.