Myofilament protein carbonylation contributes to the contractile dysfunction in the infarcted LV region of mouse hearts

Cardiovasc Res. 2014 Jan 1;101(1):108-19. doi: 10.1093/cvr/cvt236. Epub 2013 Oct 14.


Aims: 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.

Methods and 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.

Conclusion: 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.

Keywords: Contractile function; Infarction; Myocytes; Remodelling; Sarcomere.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Disease Models, Animal
  • Female
  • Mice
  • Muscle Proteins / metabolism*
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / physiopathology
  • Myocytes, Cardiac / physiology*
  • Protein Carbonylation
  • Troponin I / metabolism
  • Ventricular Function, Left
  • Ventricular Remodeling*


  • Muscle Proteins
  • Troponin I
  • Calcium