Thorac Cardiovasc Surg 2014; 62 - SC182
DOI: 10.1055/s-0034-1367443

Cannabinoid receptor CB2 delays development of cardiac failure caused by pressure overload in a murine model of transverse aortic constriction

G.D. Dürr 1, J.C. Heinemann 1, J. Kley 1, A. Ottersbach 2, W. Röll 1, A. Zimmer 3, B. Lutz 4, A. Welz 1, O. Dewald 1
  • 1Klinik und Poliklinik für Herzchirurgie, Universitätsklinikum, Bonn, Germany
  • 2Institut für Physiologie I, Life&Brain Center, Universität, Bonn, Germany
  • 3Institut für molekulare Psychiatrie, Life&Brain Center, Universität, Bonn, Germany
  • 4Institut für physiologische Chemie, Universitätsklinikum, Mainz, Germany

Purpose: Inflammatory reaction has been experimentally associated with cardiac adaptation to pressure overload leading to myocardial fibrosis and heart failure. We have recently demonstrated that endogenous cannabinoids and the cannabinoid receptor 2 (CB2) are activated and accompanied by persistent inflammation in myocardium of patients with aortic valve stenosis. Therefore, we investigated the role of the CB2 in a pressure overload mouse model.

Methods: Transverse aortic constriction was performed in CB2−/−-mice and their wildtype littermates (CB2+/+; n>8/group). After M-mode echocardiography and Millar® pressure-volume left ventricular catheter measurements at days 7 and 21, hearts were harvested and subjected to immunohistochemical and Taqman® RT-qPCR analysis.

Results: Collagen area measurements using picrosirius red planimetry revealed a significantly larger collagen deposition in CB2−/−-mice after 7 and 21 days, and this deposition resulted morphologically in more frequent confluent infarcted areas with cardiomyocyte loss than in CB2+/+ mice. Functional evaluation revealed early development of ventricular dysfunction in CB2−/−-mice after 7 days, while both genotypes had comparable dysfunction level after 21 days. Heart weight/tibia length-ratio as hypertrophy parameter was significantly higher in CB2−/−-mice after 7 days, and then comparable between the genotypes after 21 days. Macrophage density was significantly higher in CB2−/−-mice after 7 days than in CB2+/+, and it decreased in both genotypes after 21 days. Preliminary data of chemokine and cytokine mRNA-expression showed delayed modulation of inflammatory response in CB2−/−-mice after 7 days when compared to their littermates.

Conclusions: Our study suggests a cardioprotective mechanism of CB2 receptor being associated with modulation of inflammatory response and subsequent development of left ventricular dysfunction in a murine model of transverse aortic constriction.