Abstract 17610: Cannabinoid Receptor CB2 Provides Cardioprotection in a Murine Model of Pressure Overload

• Published in: Circulation (New York, N.Y.) N.Y.), 2016-11, Vol.134 (Suppl_1 Suppl 1), p.A17610-A17610
• Main Authors: Duerr, Georg D, Heinemann, Jan C, Kley, Julian, Roell, Wilhelm, Ottersbach, Annika, Zimmer, Andreas, Lutz, Beat, Dewald, Oliver
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539

IntroductionMyocardial pressure overload induces hypertrophy and is associated with inflammatory reaction and fibrosis. Hypertrophic myocardium in patients with aortic stenosis shows activation of endogenous cannabinoids and the cannabinoid receptor 2 (CB2).HypothesisWe postulated a cardioprotective role for CB2 receptor during adaptation to pressure overload.MethodsMyocardial hypertrophy was induced in CB2/-mice and their wild type littermates (CB2/; n=8-12/group) using transverse aortic constriction. Functional measurements (echocardiography and Millar catheter) at days 7 and 21 were followed by immunohistochemical analysis. Taqman RT-qPCR analysis was performed after 3 and 7 days.ResultsThe extent of hypertrophy (heart weight/tibia length-ratio and cardiomyocyte diameter) was comparable between CB2/-mice and their littermates after 7 and 21 days. Functional analysis revealed significantly worse left ventricular function in CB2/-mice compared to their littermates after 21 days. Interstitial fibrosis was associated with significantly lower collagen deposition in CB2/ mice when compared to intramural confluent infarcted areas of CB2/-mice, which also showed increased apoptosis. CB2/-mice had significantly higher macrophage and myofibroblast density after 7 days. Molecular analysis revealed maladaptation of cardiac contractile elements, prolonged inflammatory reaction and its delayed resolution in CB2/-mice. The endocannabinoid system showed significantly higher anandamide production and CB2 receptor expression in Cnr2 mice, and a compensatory induction of the CB1 receptor in Cnr2 mice.ConclusionsOur data suggest a cardioprotective role of CB2 receptor being associated with modulation of contractile elements in cardiomyocytes, inflammatory response and myocardial remodeling during adaptation to pressure overload in a murine model of transverse aortic constriction.