title: Myofilament protein carbonylation contributes to the contractile dysfunction in the infarcted LV region of mouse hearts.
abstract: OBJECTIVE
  The region-specific mechanical function of left ventricular (LV) murine cardiomyocytes and the role of phosphorylation and oxidative modifications of myofilament proteins were investigated in the process of post-myocardial infarction (MI) remodelling 10 weeks after ligation of the left anterior descending (LAD) coronary artery.
  
  
  RESULTS
  Permeabilized murine cardiomyocytes from the remaining anterior and a remote non-infarcted inferior LV area were compared with those of non-infarcted age-matched controls. Myofilament phosphorylation, sulfhydryl (SH) oxidation, and carbonylation were also assayed. Ca(2+) sensitivity of force production was significantly lower in the anterior wall (pCa50: 5.81 ± 0.03, means ± SEM, at 2.3 µm sarcomere length) than that in the controls (pCa50: 5.91 ± 0.02) or in the MI inferior area (pCa50: 5.88 ± 0.02). The level of troponin I phosphorylation was lower and that of myofilament protein SH oxidation was higher in the anterior location relative to controls, but these changes did not explain the differences in Ca(2+) sensitivities. On the other hand, significantly higher carbonylation levels, [e.g. in myosin heavy chain (MHC) and actin] were observed in the MI anterior wall [carbonylation index (CI), CIMHC: 2.06 ± 0.46, CIactin: 1.46 ± 0.18] than in the controls (CI: 1). In vitro Fenton-based myofilament carbonylation in the control cardiomyocytes also decreased the Ca(2+) sensitivity of force production irrespective of the phosphorylation status of the myofilaments. Furthermore, the Ca(2+) sensitivity correlated strongly with myofilament carbonylation levels in all investigated samples.
  
  
  CONCLUSIONS
  Post-MI myocardial remodelling involves increased myofibrillar protein carbonylation and decreased Ca(2+) sensitivity of force production, leading potentially to contractile dysfunction in the remaining cardiomyocytes of the infarcted area.
authors.affiliation: Division of Clinical Physiology, Research Center for Molecular Medicine, Institute of Cardiology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Móricz Zs. krt. 22, Debrecen H-4032, Hungary.
authors.forename: Agnes
authors.initials: A
authors.lastname: Balogh
authors.forename: David
authors.initials: D
authors.lastname: Santer
authors.forename: Eniko T
authors.initials: ET
authors.lastname: Pásztor
authors.forename: Attila
authors.initials: A
authors.lastname: Tóth
authors.forename: Dániel
authors.initials: D
authors.lastname: Czuriga
authors.forename: Bruno K
authors.initials: BK
authors.lastname: Podesser
authors.forename: Karola
authors.initials: K
authors.lastname: Trescher
authors.forename: Kornelia
authors.initials: K
authors.lastname: Jaquet
authors.forename: Ferenc
authors.initials: F
authors.lastname: Erdodi
authors.forename: István
authors.initials: I
authors.lastname: Edes
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Papp
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000502:physiology*; D050050:Protein Carbonylation; D019210:Troponin I / Q000378:metabolism; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D009124:Muscle Proteins; D019210:Troponin I; D002118:Calcium
keywords: Contractile function; Infarction; Myocytes; Remodelling; Sarcomere