European Heart Journal Advance Access originally published online on April 3, 2008
European Heart Journal 2008 29(9):1168-1180; doi:10.1093/eurheartj/ehn136
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Description of a local cardiac adiponectin system and its deregulation in dilated cardiomyopathy
1 Department of Cardiology and Pneumology, Campus Benjamin Franklin, Charité University Medicine Berlin, Hindenburgdamm 30, 12200 Berlin, Germany
2 Center for Cardiovascular Research, Charité University Medicine Berlin, Hessische Strasse 3–4, 10117 Berlin, Germany
3 Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany
Received 26 September 2007; revised 29 February 2008; accepted 10 March 2008; online publish-ahead-of-print 3 April 2008.
* Corresponding author. Tel: +49 30 8445 2383, Fax: +49 30 8445 3565, Email: skurkc{at}yahoo.com
Aims: Despite recent advances in medical therapy, heart failure remains a leading cause for cardiovascular mortality, and its complex pathogenesis is incompletely understood. This study was performed to identify possible new therapeutic targets in dilated cardiomyopathy (DCM).
Methods and results: Oligonucleotide microarray analysis was performed on endomyocardial biopsies (EMBs) from patients with early DCM (LVEDD 
55 mm, LVEF 
55%, n = 5) and control subjects (LVEDD < 55 mm, LVEF > 60%, no cardiac pathology, n = 4). Adiponectin, an adipocytokine involved in cellular metabolism, survival, and immunmodulation, was six-fold downregulated in DCM patients. Microarray data for adiponectin were confirmed by TaqMan-PCR (9.2-fold downregulation, control n= 9 vs. DCM n= 9, respectively, P < 0.05). Immunohistological analysis of EMBs showed significant downregulation of cardiac adiponectin protein expression independent of serum adiponectin (P = 0.36, ns) or serum TNF
concentrations (P = 0.46, ns). Neither the adiponectin receptor 1 (adipo-R1) nor adipo-R2 was deregulated in early DCM. Adiponectin mRNA and protein downregulation were confirmed in explanted hearts of patients with advanced DCM (LVEF < 25%, n= 8). In vitro, adiponectin incubation of neonatal rat ventricular myocytes led to activation of the pro-survival kinase PKB/Akt, increased eNOS-phosphorylation, and prevented stress-induced apoptosis of cardiomyocytes in an Akt-dependent manner. Moreover, inhibition of adiponectin secretion was accompanied by an increase in the expression of the cytokine and its receptors.
Conclusion: These data indicate the existence of a local cardiac adiponectin system regulated independent of adiponectin and TNF serum levels and its disturbance in cardiac pathology. The study suggests a role for adiponectin in the pathogenesis of DCM and implicates the adipocytokine as a possible future therapeutic target in DCM.
Key Words: Dilated cardiomyopathy • Adiponectin • Adiponectin receptors • Heart failure
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Kis, C. Murdoch, M. Zhang, A. Siva, S. Rodriguez-Cuenca, S. Carobbio, A. Lukasik, M. Blount, S. O'Rahilly, S. L. Gray, et al. Defective peroxisomal proliferators activated receptor gamma activity due to dominant-negative mutation synergizes with hypertension to accelerate cardiac fibrosis in mice Eur J Heart Fail, June 1, 2009; 11(6): 533 - 541. [Abstract] [Full Text] [PDF]
|
|