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.

Inhaled Carbon Monoxide Confers Antiinflammatory Effects against Ventilator-induced Lung Injury

“…The p38 MAPK is known to regulate TNF-␣ and IL-10 (37, 38) production. Although the molecular mechanism by which CO affects p38 MAPK to produce less TNF-␣ and more IL-10 needs to be further investigated, CO may have a posttranscriptional effect on TNF-␣ production (38).…”

Carbon Monoxide-Induced Early Thrombolysis Contributes to Heme Oxygenase-1-Mediated Inhibition of Neointimal Growth after Vascular Injury in Hypercholesterolemic Mice

“…Further experiments demonstrated that CO exhibited similar suppressive effect on PAI-1 expression in injured vessels, indicating that CO mediates the effect of HO-1. A study by Otterbein et al has demonstrated that CO could prevent vascular injury associated with chronic graft rejection without affecting the arterial PAI-1 expression [18]. It is speculative that CO may exhibit differential effects on arterial PAI-1 expression induced by various insults.…”

Clinical Restenosis after Coronary Stent Implantation Is Associated with the Heme Oxygenase-1 Gene Promoter Polymorphism and the Heme Oxygenase-1 +99G/C Variant

“…CO in particular has been associated with a profound inhibition of graft leukocyte infiltration/activation as well as with the inhibition of smooth muscle cell proliferation (17 ). The antiinflammatory and antiproliferative effects of CO have been successfully applied in experimental mouse models to prevent acute and long-term transplant rejection and lipopolysaccharide-induced shock or development of arteriosclerotic lesions after transplantation.…”