title: Myocardial cytokine gene expression is higher in aortic stenosis than in idiopathic dilated cardiomyopathy.
abstract: OBJECTIVE
  To investigate cytokine gene expression in patients with aortic valve stenosis (AS) and with idiopathic dilated cardiomyopathy (DCM), and to correlate wall stress with myocardial proinflammatory cytokine gene expression.
  
  
  METHODS
  Human left ventricular (LV) myocardial biopsies were obtained for subsequent reverse transcription polymerase chain reaction of tumour necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6 mRNA. The study population consisted of 24 patients with AS and 10 patients with idiopathic DCM.
  
  
  RESULTS
  Patients with AS had a larger ejection fraction (56 (5) v 37 (4)%, p < 0.01), smaller LV end diastolic volumes (146 (11) v 267 (21) ml, p < 0.01), and lower end systolic wall stress (44 (7) v 112 (11) kdyn/cm2, p < 0.001). Upregulation of TNFalpha, IL-1beta, and IL-6 gene expression was detected in both groups. However, TNFalpha gene expression was significantly higher in AS than in DCM (p = 0.009). No correlation was found between haemodynamic parameters and TNFalpha gene expression. In patients with AS there was a strong inverse relation between circulating TNFalpha and TNFalpha gene expression (r = -0.685, p = 0.014), between circulating TNFalpha and IL-1beta gene expression (r = -0.664, p = 0.018), and between soluble TNF receptor 2 and TNFalpha gene expression (r = -0.685, p = 0.020). Myocardial gene expression of TNFalpha was significantly higher in patients with well compensated AS than in patients with decompensated AS (p = 0.017). Similarly, patients with decompensated DCM were characterised by significantly lower TNFalpha gene expression than were patients with well compensated DCM (p = 0.011).
  
  
  CONCLUSIONS
  TNFalpha gene expression is significantly higher in patients with pressure overload than in normal hearts, in patients with idiopathic DCM, and in patients with compensated versus decompensated heart failure. Secondly, in patients with AS proinflammatory cytokine gene expression did not affect systolic performance. The higher TNFalpha gene expression in patients with compensated heart failure suggests that cytokine gene expression has an adaptive role in the early phase of LV remodelling.
authors.affiliation: Cardiovascular Centre, Onze Lieve Vrouw Ziekenhuis, Moorselbaan 164, 9400 Aalst, Belgium. marc.vanderheyden@olvz-aalst.be
authors.forename: M
authors.initials: M
authors.lastname: Vanderheyden
authors.forename: W J
authors.initials: WJ
authors.lastname: Paulus
authors.forename: M
authors.initials: M
authors.lastname: Voss
authors.forename: P
authors.initials: P
authors.lastname: Knuefermann
authors.forename: N
authors.initials: N
authors.lastname: Sivasubramanian
authors.forename: D
authors.initials: D
authors.lastname: Mann
authors.forename: G
authors.initials: G
authors.lastname: Baumgarten
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D002303:Cardiac Output, Low / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000235:genetics / Q000503:physiopathology
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha