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

Nat Med. 2003 Feb;9(2):183-90. doi: 10.1038/nm817. Epub 2003 Jan 21.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angioplasty, Balloon, Coronary / adverse effects*
  • Animals
  • Arteriosclerosis / prevention & control*
  • Carbon Monoxide / pharmacology*
  • Cyclic GMP / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • Enzyme Activation
  • Graft Rejection / prevention & control*
  • Guanylate Cyclase / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • Nitric Oxide Synthase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • p38 Mitogen-Activated Protein Kinases


  • Cdkn1a protein, mouse
  • Cdkn1a protein, rat
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Carbon Monoxide
  • Nitric Oxide Synthase
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Guanylate Cyclase
  • Cyclic GMP