Activation of endocannabinoid system in human myocardial hypertrophy

Objectives: The role of endocannabinoid system has been associated with cardioprotection, inflammation and fibrosis. Experimental studies showed a role for inflammation and active remodelling in myocardial hypertrophy. Therefore, we investigated the association of endocannabinoid system with myocardial hypertrophy in patients with aortic stenosis.

Methods: Myocardial biopsies were collected from patients with aortic stenosis (AS) and atrial myxoma as controls during surgery. We performed histological and molecular analysis of endocannabinoids, their receptors, inflammatory and remodelling-related cells and mediators.

Results: Myxoma patients showed a normal cardiomyocyte diameter as compared to the significantly higher diameter in AS patients. AS patients had significantly higher concentration of endocannabinoid anandamide and expression of its degrading enzyme FAAH. mRNA-expression of cannabinoid receptor CB2 was also significantly increased while it was predominantly located on cardiomyocytes. AS patients presented with compensated myocardial adaptation to pressure overload. Macrophages and newly recruited leukocytes cell densities were higher in AS than in myxoma group. Also, AS showed increased expression of chemokine IL-8 and suppression of anti-inflammatory IL-10 indicating persistent inflammatory reaction, which was not found in myxoma samples. We found higher myofibroblast density and stronger tenascin C staining along with mRNA induction of tenascin C and CTGF in AS patients showing active myocardial remodelling.

Conclusions: We demonstrate for the first time activation of endocannabinoid system and predominant expression of its receptor CB2 on cardiomyocytes in patients with AS. This is associated with persistent inflammation and active remodelling in hypertrophic myocardium.