title: Myocardial expression of fas and recovery of left ventricular function in patients with recent-onset cardiomyopathy.
abstract: OBJECTIVE
  This study aimed to evaluate the role of gene expression for predicting myocardial recovery in recent-onset cardiomyopathy.
  
  
  BACKGROUND
  Apoptosis may limit ventricular recovery. We examined the myocardial expression of Fas, Fas ligand (FasL), tumor necrosis factor (TNF)-alpha, and TNF receptor 1 (TNFR1), and myocardial recovery in patients from the multicenter Intervention in Myocarditis and Acute Cardiomyopathy (IMAC) study.
  
  
  METHODS
  Endomyocardial biopsy samples were obtained in 20 patients with recent-onset (<6 months) idiopathic dilated cardiomyopathy (left ventricular ejection fraction [LVEF] < or =0.40). The LVEF was assessed at baseline and at 6 and 12 months by nuclear scans. Myocardial expression was assessed by ribonuclease (RNase) protection, normalized to a constitutively active gene (glyceraldehydes 3-phosphate dehydrogenase [GAPDH]) and reported as percent GAPDH expression. The change in LVEF at 6 and 12 months was compared by tertiles of expression.
  
  
  RESULTS
  For all patients (14 men, 6 women; age 46.5 +/- 10.7 years), the mean LVEF was 0.28 +/- 0.05 at baseline and 0.40 +/- 0.14 at six months. Patients in the highest tertile of Fas expression had minimal improvement at six months (DeltaEF = 0.03 +/- 0.05) when compared with the intermediate (DeltaEF = 0.10 +/- 0.13) and lowest tertiles (DeltaEF = 0.21 +/- 0.11, change in LVEF by tertile, p = 0.006). A similar relationship was seen with TNFR1 expression (highest tertile, DeltaEF = 0.06 +/- 0.07; lowest tertile, DeltaEF = 0.21 +/- 0.11, p = 0.02). In contrast with Fas and TNFR1, expression of TNF-alpha and FasL did not predict recovery of LV function.
  
  
  CONCLUSIONS
  In cardiomyopathy of recent onset, increased expression of Fas and TNFR1 was associated with minimal recovery of LV function. Apoptosis limits myocardial recovery, and represents a potential target for therapeutic intervention.
authors.affiliation: McGill University, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Sheppard
authors.forename: Maninder
authors.initials: M
authors.lastname: Bedi
authors.forename: Toru
authors.initials: T
authors.lastname: Kubota
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Semigran
authors.forename: William
authors.initials: W
authors.lastname: Dec
authors.forename: Richard
authors.initials: R
authors.lastname: Holubkov
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Feldman
authors.forename: Warren D
authors.initials: WD
authors.lastname: Rosenblum
authors.forename: Charles F
authors.initials: CF
authors.lastname: McTiernan
authors.forename: Dennis M
authors.initials: DM
authors.lastname: McNamara
mesh_terms: D000328:Adult; D009202:Cardiomyopathies / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000096:biosynthesis*; D020127:Recovery of Function; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D048069:Tumor Necrosis Factors / Q000096:biosynthesis*; D016277:Ventricular Function, Left; D019014:fas Receptor / Q000096:biosynthesis*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D019014:fas Receptor