title: Oxidation of myofibrillar proteins in human heart failure.
abstract: OBJECTIVE
  We investigated the incidence and contribution of the oxidation/nitrosylation of tropomyosin and actin to the contractile impairment and cardiomyocyte injury occurring in human end-stage heart failure (HF) as compared with nonfailing donor hearts.
  
  
  BACKGROUND
  Although there is growing evidence that augmented intracellular accumulation of reactive oxygen/nitrogen species may play a key role in causing contractile dysfunction, there is a dearth of data regarding their contractile protein targets in human HF.
  
  
  METHODS
  In left ventricular (LV) biopsies from explanted failing hearts (New York Heart Association functional class IV; HF group) and nonfailing donor hearts (NF group), carbonylation of actin and tropomyosin, disulphide cross-bridge (DCB) formation, and S-nitrosylation in tropomyosin were assessed, along with plasma troponin I and LV ejection fraction (LVEF).
  
  
  RESULTS
  The LV biopsies from the HF group had 2.14 ± 0.23-fold and 2.31 ± 0.46-fold greater levels in actin and tropomyosin carbonylation, respectively, and 1.77 ± 0.45-fold greater levels of high-molecular-weight complexes of tropomyosin due to DCB formation, compared with the NF group. Tropomyosin also underwent S-nitrosylation that was 1.3 ± 0.15-fold higher in the HF group. Notably, actin and tropomyosin carbonylation was significantly correlated with both loss of viability indicated by plasma troponin I and contractile impairment as shown by reduced LVEF.
  
  
  CONCLUSIONS
  This study demonstrated that oxidative/nitrosylative changes of actin and tropomyosin are largely increased in human failing hearts. Because these changes are inversely correlated to LVEF, actin and tropomyosin oxidation are likely to contribute to the contractile impairment evident in end-stage HF.
authors.affiliation: Department of Biomedical Sciences, University of Padova, Italy. marcella.canton@unipd.it
authors.forename: Marcella
authors.initials: M
authors.lastname: Canton
authors.forename: Sara
authors.initials: S
authors.lastname: Menazza
authors.forename: Freya L
authors.initials: FL
authors.lastname: Sheeran
authors.forename: Patrizia
authors.initials: P
authors.lastname: Polverino de Laureto
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Lisa
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pepe
mesh_terms: D000199:Actins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D003285:Contractile Proteins / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014335:Tropomyosin / Q000378:metabolism*
chemical_list: D000199:Actins; D003285:Contractile Proteins; D017382:Reactive Oxygen Species; D014335:Tropomyosin