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.
