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 types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Angioplasty, Balloon, Coronary / adverse effects*
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Animals
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Arteriosclerosis / prevention & control*
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Carbon Monoxide / pharmacology*
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Cyclic GMP / metabolism
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / metabolism
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Enzyme Activation
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Graft Rejection / prevention & control*
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Guanylate Cyclase / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mitogen-Activated Protein Kinases / metabolism
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Nitric Oxide Synthase / metabolism
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Rats
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Rats, Sprague-Dawley
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p38 Mitogen-Activated Protein Kinases
Substances
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Cdkn1a protein, mouse
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Cdkn1a protein, rat
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Carbon Monoxide
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Nitric Oxide Synthase
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Guanylate Cyclase
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Cyclic GMP