title: Autonomic dysfunction in patients with arrhythmogenic right ventricular cardiomyopathy: biochemical evidence of altered signaling pathways.
abstract: BACKGROUND
  Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden cardiac death especially in times of increased sympathetic tone, for example, during sports, which have been confirmed by nuclear imaging studies. However, the underlying biochemical pathways remain to be delineated. Therefore, we investigated the expression levels of proteins of the signaling cascade in patients with ARVC.
  
  
  METHODS
  During diagnostic work-up, right ventricular endomyocardial biopsies (EMBs) were sampled from 15 consecutive male ARVC patients (52 ± 14 years). Tissue levels of key proteins of the signaling cascade were analyzed. Results were compared to those obtained from EMBs of 10 patients with idiopathic right ventricular outflow-tract tachycardia (RVOT; 41 ± 14 years) and of five control subjects without identifiable structural heart disease (42 ± 13 years; P = ns).
  
  
  RESULTS
  Among the proteins analyzed, only tissue levels of norepinephrine (NE; P < 0.04) and cyclic adenosine-3´,5´-monophospate (cAMP; P < 0.01) were significantly lower in ARVC when compared to RVOT patients. When compared to controls, mean cAMP levels were lower in patients with ARVC but did not reach statistical significance. No differences in cAMP were observed between RVOT and controls.
  
  
  CONCLUSIONS
  The current findings confirm and expand the concept of adrenergic dysfunction in ARVC: the reduction of NE in ARVC could lead to an impaired stimulation of β-adrenoceptor subsequent signaling pathways with potential implication for cardiac fibrosis and arrhythmogenesis.
authors.affiliation: Department of Cardiology and Angiology, University Hospital Münster, Münster, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Paul
authors.forename: Matthias
authors.initials: M
authors.lastname: Meyborg
authors.forename: Peter
authors.initials: P
authors.lastname: Boknik
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gergs
authors.forename: Joachim
authors.initials: J
authors.lastname: Gerss
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schmitz
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.forename: Thomas
authors.initials: T
authors.lastname: Wichter
authors.forename: Joachim
authors.initials: J
authors.lastname: Neumann
mesh_terms: D000328:Adult; D000368:Aged; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000150:complications* / Q000378:metabolism*; D001342:Autonomic Nervous System Diseases / Q000150:complications* / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000242:Cyclic AMP; D009638:Norepinephrine
keywords: arrhythmogenic right ventricular cardiomyopathy; autonomic nervous system; signaling pathway