title: Adiponectin expression in patients with inflammatory cardiomyopathy indicates favourable outcome and inflammation control.
abstract: OBJECTIVE
  Circulating adiponectin (APN) is an immunomodulatory, pro-angiogenic, and anti-apoptotic adipocytokine protecting against acute viral heart disease and preventing pathological remodelling after cardiac injury. The purpose of this study was to describe the regulation and effects of APN in patients with inflammatory cardiomyopathy (DCMi).
  
  
  RESULTS
  Adiponectin expression and outcome were assessed in 173 patients with DCMi, 30 patients with non-inflammatory DCM, and 30 controls. Mechanistic background of these findings was addressed in murine experimental autoimmune myocarditis (EAM), a model of human DCMi, and further elucidated in vitro. Adiponectin plasma concentrations were significantly higher in DCMi compared with DCM or controls, i.e. 6.8 ± 3.9 µg/mL vs. 5.4 ± 3.6 vs. 4.76 ± 2.5 µg/mL (P< 0.05, respectively) and correlated significantly with cardiac mononuclear infiltrates (CD3+: r(2)= 0.025, P= 0.038; CD45R0+: r(2)= 0.058, P= 0.018). At follow-up, DCMi patients with high APN levels showed significantly increased left ventricular ejection fraction improvement, decreased left ventricular end-diastolic diameter, and reduced cardiac inflammatory infiltrates compared with patients with low APN levels. A multivariate linear regression analysis implicated APN as an independent prognostic factor for inhibition of cardiac inflammation. In accordance with these findings in human DCMi, EAM mice exhibited elevated plasma APN. Adiponectin gene transfer led to significant downregulation of key inflammatory mediators promoting disease. Mechanistically, APN acted as a negative regulator of T cells by reducing antigen specific expansion (P< 0.01) and suppressed TNFα-mediated NFκB activation (P< 0.01) as well as release of reactive oxygen species in cardiomyocytes.
  
  
  CONCLUSIONS
  Our results implicate that APN acts as endogenously upregulated anti-inflammatory cytokine confining cardiac inflammation and progression in DCMi.
authors.affiliation: Department of Cardiology and Pneumology, Charité-University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bobbert
authors.forename: Carmen
authors.initials: C
authors.lastname: Scheibenbogen
authors.forename: Alexander
authors.initials: A
authors.lastname: Jenke
authors.forename: Gabriele
authors.initials: G
authors.lastname: Kania
authors.forename: Sabrina
authors.initials: S
authors.lastname: Wilk
authors.forename: Stefanie
authors.initials: S
authors.lastname: Krohn
authors.forename: Jenny
authors.initials: J
authors.lastname: Stehr
authors.forename: Uwe
authors.initials: U
authors.lastname: Kuehl
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauch
authors.forename: Urs
authors.initials: U
authors.lastname: Eriksson
authors.forename: Heinz Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Poller
authors.forename: Carsten
authors.initials: C
authors.lastname: Skurk
mesh_terms: D052242:Adiponectin / Q000378:metabolism* / Q000502:physiology; D000328:Adult; D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005500:Follow-Up Studies; D018014:Gene Transfer Techniques; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009205:Myocarditis / Q000378:metabolism* / Q000503:physiopathology; D016328:NF-kappa B / Q000378:metabolism; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D015854:Up-Regulation
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D016207:Cytokines; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha