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

Ágnes Balogh, David Santer, Enik T. Pásztor, Attila Tóth, Dániel Czuriga, Bruno K. Podesser, Karola Trescher, Kornelia Jaquet, F. Erdődi, I. Édes, Z. Papp

Research output: Contribution to journalArticle

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Abstract

AimsThe 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 resultsPermeabilized 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 m 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, CI actin: 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.ConclusionPost-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.

Original languageEnglish
Pages (from-to)108-119
Number of pages12
JournalCardiovascular Research
Volume101
Issue number1
DOIs
Publication statusPublished - Jan 1 2014

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Protein Carbonylation
Myofibrils
Cardiac Myocytes
Phosphorylation
Actins
Myocardial Infarction
Anterior Wall Myocardial Infarction
Inferior Wall Myocardial Infarction
Sarcomeres
Troponin I
Myosin Heavy Chains
Oxidative Phosphorylation
Left Ventricular Function
Ligation
Coronary Vessels
Proteins

Keywords

  • Contractile function
  • Infarction
  • Myocytes
  • Remodelling
  • Sarcomere

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Myofilament protein carbonylation contributes to the contractile dysfunction in the infarcted LV region of mouse hearts. / Balogh, Ágnes; Santer, David; Pásztor, Enik T.; Tóth, Attila; Czuriga, Dániel; Podesser, Bruno K.; Trescher, Karola; Jaquet, Kornelia; Erdődi, F.; Édes, I.; Papp, Z.

In: Cardiovascular Research, Vol. 101, No. 1, 01.01.2014, p. 108-119.

Research output: Contribution to journalArticle

Balogh, Ágnes ; Santer, David ; Pásztor, Enik T. ; Tóth, Attila ; Czuriga, Dániel ; Podesser, Bruno K. ; Trescher, Karola ; Jaquet, Kornelia ; Erdődi, F. ; Édes, I. ; Papp, Z. / Myofilament protein carbonylation contributes to the contractile dysfunction in the infarcted LV region of mouse hearts. In: Cardiovascular Research. 2014 ; Vol. 101, No. 1. pp. 108-119.
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abstract = "AimsThe 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 resultsPermeabilized 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 m 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, CI actin: 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.ConclusionPost-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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AU - Santer, David

AU - Pásztor, Enik T.

AU - Tóth, Attila

AU - Czuriga, Dániel

AU - Podesser, Bruno K.

AU - Trescher, Karola

AU - Jaquet, Kornelia

AU - Erdődi, F.

AU - Édes, I.

AU - Papp, Z.

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N2 - AimsThe 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 resultsPermeabilized 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 m 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, CI actin: 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.ConclusionPost-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.

AB - AimsThe 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 resultsPermeabilized 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 m 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, CI actin: 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.ConclusionPost-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.

KW - Contractile function

KW - Infarction

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KW - Remodelling

KW - Sarcomere

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