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The cannabinoid receptor type 2 promotes cardiac myocyte and fibroblast survival and protects against ischemia/reperfusion-induced cardiomyopathy.: CB2 in ischemic cardiomyopathy

Abstract : 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.
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https://www.hal.inserm.fr/inserm-00371859
Contributor : Georges Guellaen <>
Submitted on : Monday, March 30, 2009 - 4:04:10 PM
Last modification on : Wednesday, August 19, 2020 - 11:17:01 AM
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Nicole Defer, Jinghong Wan, Richard Souktani, Brigitte Escoubet, Magali Perier, et al.. The cannabinoid receptor type 2 promotes cardiac myocyte and fibroblast survival and protects against ischemia/reperfusion-induced cardiomyopathy.: CB2 in ischemic cardiomyopathy. FASEB Journal, Federation of American Society of Experimental Biology, 2009, 23 (7), pp.2120-30. ⟨10.1096/fj.09-129478⟩. ⟨inserm-00371859⟩

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