title: Myocardial hypertrophy is associated with inflammation and activation of endocannabinoid system in patients with aortic valve stenosis.
abstract: OBJECTIVE
  Endocannabinoids and their receptors have been associated with cardiac adaptation to injury, inflammation and fibrosis. Experimental studies suggested a role for inflammatory reaction and active remodeling in myocardial hypertrophy, but they have not been shown in human hypertrophy. We investigated the association of the 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. Histological and molecular analysis of endocannabinoids and their receptors, inflammatory and remodeling-related cells and mediators was performed.
  
  
  RESULTS
  Myocardial hypertrophy was confirmed with significantly higher cardiomyocyte diameter in AS than in myxoma patients, which had normal cell size. AS patients presented compensated myocardial adaptation to pressure overload. AS patients had significantly higher: concentration of endocannabinoid anandamide, expression of its degrading enzyme FAAH, and of cannabinoid receptor CB2, being predominantly located on cardiomyocytes. Cell density of macrophages and newly recruited leukocytes were higher in AS group, which together with increased expression of chemokines CCL2, CCL4 and CXCL8, and suppression of anti-inflammatory IL-10 indicates persistent inflammatory reaction. 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 remodeling.
  
  
  CONCLUSIONS
  Our study shows for the first time activation of the endocannabinoid system and predominant expression of its receptor CB2 on cardiomyocytes being associated with persistent inflammation and active remodeling in hypertrophic myocardium of patients with aortic stenosis.
authors.affiliation: Department of Cardiac Surgery, University Clinical Center Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
authors.forename: Georg D
authors.initials: GD
authors.lastname: Duerr
authors.forename: Jan C
authors.initials: JC
authors.lastname: Heinemann
authors.forename: Silke
authors.initials: S
authors.lastname: Dunkel
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.forename: Raissa
authors.initials: R
authors.lastname: Lerner
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Roell
authors.forename: Fritz
authors.initials: F
authors.lastname: Mellert
authors.forename: Chris
authors.initials: C
authors.lastname: Probst
authors.forename: Bahman
authors.initials: B
authors.lastname: Esmailzadeh
authors.forename: Armin
authors.initials: A
authors.lastname: Welz
authors.forename: Oliver
authors.initials: O
authors.lastname: Dewald
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000150:complications* / Q000378:metabolism; D006332:Cardiomegaly / Q000150:complications* / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism; D008297:Male
chemical_list: D063388:Endocannabinoids