Abstract 17610: Cannabinoid Receptor CB2 Provides Cardioprotection in a Murine Model of Pressure Overload
Introduction: Myocardial 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).
Hypothesis: We postulated a cardioprotective role for CB2 receptor during adaptation to pressure overload.
Methods: Myocardial 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.
Results: The 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.
Conclusions: Our 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.
Author Disclosures: G.D. Duerr: None. J.C. Heinemann: None. J. Kley: None. W. Roell: None. A. Ottersbach: None. A. Zimmer: None. B. Lutz: None. O. Dewald: None.
- © 2016 by American Heart Association, Inc.