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

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

Agnes Balogh  1 , David Santer, Eniko T Pásztor, Attila Tóth, Dániel Czuriga, Bruno K Podesser, Karola Trescher, Kornelia Jaquet, Ferenc Erdodi, István Edes, Zoltán Papp
Affiliations

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

Agnes Balogh et al. Cardiovasc Res. .

Abstract

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.

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