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

Balogh, Ágnes; Santer, David; Pásztor, Enikő T.; Tóth, Attila; Czuriga, Dániel; Podesser, Bruno K.; Trescher, Karola; Jaquet, Kornelia; Erdődi, Ferenc; Édes, István; Papp, Zoltán
January 2014
Cardiovascular Research;Jan2014, Vol. 101 Issue 1, p108
Academic Journal
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. Ca2+ 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 Ca2+ 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 Ca2+ sensitivity of force production irrespective of the phosphorylation status of the myofilaments. Furthermore, the Ca2+ sensitivity correlated strongly with myofilament carbonylation levels in all investigated samples. Conclusion Post-MI myocardial remodelling involves increased myofibrillar protein carbonylation and decreased Ca2+ sensitivity of force production, leading potentially to contractile dysfunction in the remaining cardiomyocytes of the infarcted area.


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