%0 Journal Article %T The cannabinoid receptor type 2 promotes cardiac myocyte and fibroblast survival and protects against ischemia/reperfusion-induced cardiomyopathy. %T CB2 in ischemic cardiomyopathy %+ Institut Mondor de Recherche Biomédicale (IMRB) %+ Plate-forme petit animal %+ Centre de Recherche des Cordeliers (CRC (UMR_S 872)) %+ Department of Molecular Psychiatry %+ Département de chirurgie cardiaque %A Defer, Nicole %A Wan, Jinghong %A Souktani, Richard %A Escoubet, Brigitte %A Perier, Magali %A Caramelle, Philippe %A Manin, Sylvie %A Deveaux, Vanessa %A Bourin, Marie-Claude %A Zimmer, Andreas %A Lotersztajn, Sophie %A Pecker, Françoise %A Pavoine, Catherine %Z J Wan was supported by a fellowship from the Agence Nationale de la Recherche (n°R06403JS, canna licoca).This work was supported by INSERM, the Université Paris-Val de Marne, the Assistance Publique des Hopitaux de Paris (as a contrat d'interface to F.P.) and a grant from the Agence Nationale de la Recherche (n°R06403JS). %< avec comité de lecture %@ 0892-6638 %J FASEB Journal %I Federation of American Society of Experimental Biology %V 23 %N 7 %P 2120-30 %8 2009-07 %D 2009 %R 10.1096/fj.09-129478 %M 19246487 %K cannabinoids %K in vivo %K remodeling %K apoptosis %K heart failure. %K heart failure %Z Life Sciences [q-bio]/Biochemistry, Molecular BiologyJournal articles %X Post-myocardial infarction (MI) heart failure is a major public health problem in Western countries and results from ischemia/reperfusion (IR)-induced cell death, remodeling, and contractile dysfunction. Ex vivo studies have demonstrated the cardioprotective anti-inflammatory effect of the cannabinoid type 2 (CB2) receptor agonists within hours after IR. Herein, we evaluated the in vivo effect of CB2 receptors on IR-induced cell death, fibrosis, and cardiac dysfunction and investigated the target role of cardiac myocytes and fibroblasts. The infarct size was increased 24 h after IR in CB2(-/-) vs. wild-type (WT) hearts and decreased when WT hearts were injected with the CB2 agonist JWH133 (3 mg/kg) at reperfusion. Compared with WT hearts, CB2(-/-) hearts showed widespread injury 3 d after IR, with enhanced apoptosis and remodeling affecting the remote myocardium. Finally, CB2(-/-) hearts exhibited exacerbated fibrosis, associated with left ventricular dysfunction 4 wk after IR, whereas their WT counterparts recovered normal function. Cardiac myocytes and fibroblasts isolated from CB2(-/-) hearts displayed a higher H(2)O(2)-induced death than WT cells, whereas 1 microM JWH133 triggered survival effects. Furthermore, H(2)O(2)-induced myofibroblast activation was increased in CB2(-/-) fibroblasts but decreased in 1 microM JWH133-treated WT fibroblasts, compared with that in WT cells. Therefore, CB2 receptor activation may protect against post-IR heart failure through direct inhibition of cardiac myocyte and fibroblast death and prevention of myofibroblast activation. %G English %2 https://inserm.hal.science/inserm-00371859/document %2 https://inserm.hal.science/inserm-00371859/file/FJ_Pavoine.pdf %L inserm-00371859 %U https://inserm.hal.science/inserm-00371859 %~ INSERM %~ UNIV-PARIS5 %~ UPMC %~ CNRS %~ APHP %~ IMRB %~ UPEC %~ CORDELIERS %~ UPMC_POLE_4 %~ SORBONNE-UNIVERSITE %~ SU-SCIENCES %~ UNIV-PARIS %~ SU-TI %~ ANR %~ ALLIANCE-SU