Carbon monoxide: mechanisms of action and potential clinical implications.

Abstract : Small amounts of carbon monoxide (CO) are continuously produced in mammals. The intracellular levels of CO can increase under stressful conditions following the induction of HO-1 (heme oxygnase-1), a ubiquitous enzyme responsible for the catabolism of heme. Unlike nitric oxide, which is a free radical, CO does not contain free electrons but may be involved in oxidative stress. The carbonate radical has been proposed to be a key mediator of oxidative damage resulting from peroxynitrite production, likewise, the precursor of the carbonate radical anion being bicarbonate and carbon dioxide. We report herein some of the transcription factors and protein kinases involved in the regulation of vascular HO-1 expression. Beyond its widely feared toxicity, CO has revealed a very important biological activity as a signaling molecule with marked protective actions namely against apoptosis and endothelial oxidative damage. Abnormal metabolism and function of CO contribute to the pathogenesis and development of cardiovascular diseases. Important results have been reported in which CO and CO-releasing molecules (CO-RMs) prevent intimal hyperplasia by arresting hyperproliferative vascular smooth muscle cells and increased mobilization and recruitment of bone-marrow-derived progenitor cells. Clinical studies have demonstrated beneficial properties of CO-RMs in transplantation. The anti-inflammatory properties of CO and CO-RMs have been demonstrated in a multitude of animal models of inflammation, suggesting a possible therapeutic application for inflammatory diseases. The development of a technology concerning CO-RMs that controls the delivery and action of CO under different pathological conditions represents a major step forward in the development of CO-based pharmaceuticals with therapeutic applications.
Type de document :
Article dans une revue
Pharmacology and Therapeutics, Elsevier, 2013, 137 (2), pp.133-52. 〈10.1016/j.pharmthera.2012.09.007〉
Liste complète des métadonnées

Littérature citée [220 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00744757
Contributeur : Catherine Vergely <>
Soumis le : mardi 23 octobre 2012 - 17:55:57
Dernière modification le : vendredi 8 juin 2018 - 14:50:25
Document(s) archivé(s) le : samedi 17 décembre 2016 - 04:19:14

Fichiers

Carbon_monoxide_revised_SEPTEM...
Fichiers produits par l'(les) auteur(s)

Identifiants

Collections

Citation

Luc Rochette, Yves Cottin, Marianne Zeller, Catherine Vergely. Carbon monoxide: mechanisms of action and potential clinical implications.. Pharmacology and Therapeutics, Elsevier, 2013, 137 (2), pp.133-52. 〈10.1016/j.pharmthera.2012.09.007〉. 〈inserm-00744757〉

Partager

Métriques

Consultations de la notice

324

Téléchargements de fichiers

764