Decreased age-related cardiac dysfunction, myocardial nitrative stress, inflammatory gene expression, and apoptosis in mice lacking fatty acid amide hydrolase.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_292AB7F34100
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Decreased age-related cardiac dysfunction, myocardial nitrative stress, inflammatory gene expression, and apoptosis in mice lacking fatty acid amide hydrolase.
Périodique
American Journal of Physiology. Heart and Circulatory Physiology
Auteur(s)
Bátkai S., Rajesh M., Mukhopadhyay P., Haskó G., Liaudet L., Cravatt B.F., Csiszár A., Ungvári Z., Pacher P.
ISSN
0363-6135
Statut éditorial
Publié
Date de publication
08/2007
Peer-reviewed
Oui
Volume
293
Numéro
2
Pages
H909-918
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article
Résumé
Recent studies have uncovered important cross talk between inflammation, generation of reactive oxygen and nitrogen species, and lipid metabolism in the pathogenesis of cardiovascular aging. Inhibition of the endocannabinoid anandamide metabolizing enzyme, the fatty acid amide hydrolase (FAAH), is emerging as a promising novel approach for the treatment of various inflammatory disorders. In this study, we have investigated the age-associated decline of cardiac function and changes in inflammatory gene expression, nitrative stress, and apoptosis in FAAH knockout (FAAH(-/-)) mice and their wild-type (FAAH(+/+)) littermates. Additionally, we have explored the effects of anandamide on TNF-alpha-induced ICAM-1 and VCAM-1 expression and monocyte-endothelial adhesion in human coronary artery endothelial cells (HCAECs). There was no difference in the cardiac function (measured by the pressure-volume conductance catheter system) between 2- to 3-mo-old (young) FAAH(-/-) and FAAH(+/+) mice. In contrast, the aging-associated decline in cardiac function and increased myocardial gene expression of TNF-alpha, gp91phox, matrix metalloproteinase (MMP)-2, MMP-9, caspase-3 and caspase-9, myocardial inducible nitric oxide synthase protein expression, nitrotyrosine formation, poly (ADP-ribose)polymerase cleavage and caspase-3/9 activity, observed in 28- to 31-mo-old (aging) FAAH(+/+) mice, were largely attenuated in knockouts. There was no difference in the myocardial cannabinoid CB(1) and CB(2) receptor gene expression between young and aging FAAH(-/-) and FAAH(+/+) mice. Anandamide dose dependently attenuated the TNF-alpha-induced ICAM-1 and VCAM-1 expression, NF-kappaB activation in HCAECs, and the adhesion of monocytes to HCAECs in a CB(1)- and CB(2)-dependent manner. These findings suggest that pharmacological inhibition of FAAH may represent a novel protective strategy against chronic inflammation, oxidative/nitrative stress, and apoptosis associated with cardiovascular aging and atherosclerosis.
Mots-clé
Aging/genetics, Aging/metabolism, Amidohydrolases/deficiency, Amidohydrolases/genetics, Animals, Apoptosis, Arachidonic Acids/metabolism, Cell Adhesion, Cells, Cultured, Coronary Vessels/cytology, Coronary Vessels/metabolism, Endothelial Cells/metabolism, Gene Expression Regulation, Humans, Inflammation/enzymology, Inflammation/genetics, Intercellular Adhesion Molecule-1/metabolism, Mice, Mice, Knockout, Monocytes/metabolism, Myocardium/enzymology, Myocardium/metabolism, NF-kappa B/metabolism, Polyunsaturated Alkamides/metabolism, Reactive Nitrogen Species/metabolism, Receptors, Cannabinoid/metabolism, Tumor Necrosis Factor-alpha/metabolism, Vascular Cell Adhesion Molecule-1/metabolism, Ventricular Dysfunction, Left/enzymology, Ventricular Dysfunction, Left/genetics
Pubmed
Web of science
Création de la notice
24/01/2008 18:01
Dernière modification de la notice
20/08/2019 14:08
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