Epigallocatechin-3-gallate accelerates relaxation and Ca2+ transient decay and desensitizes myofilaments in healthy and Mybpc3-targeted knock-in cardiomyopathic mice
Background. Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac muscle disease with left ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction. Increased myofilament Ca2+ sensitivity could be the underlying cause of diastolic dysfunction. Epigallocatechin-3-gall...
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| Format: | Article |
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Frontiers Media S.A.
2016-12-01
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| Series: | Frontiers in Physiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00607/full |
| _version_ | 1817994564710957056 |
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| author | Felix W. Friedrich Felix W. Friedrich Frederik Flenner Frederik Flenner Mahtab Nasib Mahtab Nasib Thomas Eschenhagen Thomas Eschenhagen Lucie Carrier Lucie Carrier |
| author_facet | Felix W. Friedrich Felix W. Friedrich Frederik Flenner Frederik Flenner Mahtab Nasib Mahtab Nasib Thomas Eschenhagen Thomas Eschenhagen Lucie Carrier Lucie Carrier |
| author_sort | Felix W. Friedrich |
| collection | DOAJ |
| description | Background. Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac muscle disease with left ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction. Increased myofilament Ca2+ sensitivity could be the underlying cause of diastolic dysfunction. Epigallocatechin-3-gallate (EGCg), a catechin found in green tea has, been reported to decrease myofilament Ca2+ sensitivity in HCM models with troponin mutations. However, whether this is also the case for HCM-associated thick filament mutations is not known. Therefore, we evaluated whether EGCg affects the behavior of cardiomyocytes and myofilaments of a HCM mouse model carrying a gene mutation in cardiac myosin-binding protein C and exhibiting both increased myofilament Ca2+ sensitivity and diastolic dysfunction.Methods and Results. Acute effects of EGCg were tested on fractional sarcomere shortening and Ca2+ transients in intact ventricular myocytes and on force-Ca2+ relationship of skinned ventricular muscle strips isolated from Mybpc3-targeted knock-in (KI) and wild-type (WT) mice. Fractional sarcomere shortening and Ca2+ transients were analyzed at 37 °C under 1-Hz pacing in the absence or presence of EGCg (1.8 µM). At baseline and in the absence of Fura-2, KI cardiomyocytes displayed lower diastolic sarcomere length, higher fractional sarcomere shortening, longer time to peak shortening and time to 50% relengthening than WT cardiomyocytes. In WT and KI neither diastolic sarcomere length nor fractional sarcomere shortening were influenced by EGCg treatment, but relaxation time was reduced, to a greater extent in KI cells. EGCg shortened time to peak Ca2+ and Ca2+ transient decay in Fura-2-loaded WT and KI cardiomyocytes. EGCg did not influence phosphorylation of phospholamban. In skinned cardiac muscle strips, EGCg (30 µM) decreased Ca2+ sensitivity in both groups. Conclusion. EGCg fastened relaxation and Ca2+ transient decay to a larger extent in KI than in WT cardiomyocytes. This effect could be partially explained by myofilament Ca2+ desensitization. |
| first_indexed | 2024-04-14T01:54:41Z |
| format | Article |
| id | doaj.art-b519bb49ef43498eb4e84a49d52c185a |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-14T01:54:41Z |
| publishDate | 2016-12-01 |
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| series | Frontiers in Physiology |
| spelling | doaj.art-b519bb49ef43498eb4e84a49d52c185a2022-12-22T02:19:09ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2016-12-01710.3389/fphys.2016.00607233197Epigallocatechin-3-gallate accelerates relaxation and Ca2+ transient decay and desensitizes myofilaments in healthy and Mybpc3-targeted knock-in cardiomyopathic miceFelix W. Friedrich0Felix W. Friedrich1Frederik Flenner2Frederik Flenner3Mahtab Nasib4Mahtab Nasib5Thomas Eschenhagen6Thomas Eschenhagen7Lucie Carrier8Lucie Carrier9University Medical Center EppendorfGerman Centre for Cardiovascular Research, partner site Hamburg/Kiel/LübeckUniversity Medical Center EppendorfGerman Centre for Cardiovascular Research, partner site Hamburg/Kiel/LübeckUniversity Medical Center EppendorfGerman Centre for Cardiovascular Research, partner site Hamburg/Kiel/LübeckUniversity Medical Center EppendorfGerman Centre for Cardiovascular Research, partner site Hamburg/Kiel/LübeckUniversity Medical Center EppendorfGerman Centre for Cardiovascular Research, partner site Hamburg/Kiel/LübeckBackground. Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac muscle disease with left ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction. Increased myofilament Ca2+ sensitivity could be the underlying cause of diastolic dysfunction. Epigallocatechin-3-gallate (EGCg), a catechin found in green tea has, been reported to decrease myofilament Ca2+ sensitivity in HCM models with troponin mutations. However, whether this is also the case for HCM-associated thick filament mutations is not known. Therefore, we evaluated whether EGCg affects the behavior of cardiomyocytes and myofilaments of a HCM mouse model carrying a gene mutation in cardiac myosin-binding protein C and exhibiting both increased myofilament Ca2+ sensitivity and diastolic dysfunction.Methods and Results. Acute effects of EGCg were tested on fractional sarcomere shortening and Ca2+ transients in intact ventricular myocytes and on force-Ca2+ relationship of skinned ventricular muscle strips isolated from Mybpc3-targeted knock-in (KI) and wild-type (WT) mice. Fractional sarcomere shortening and Ca2+ transients were analyzed at 37 °C under 1-Hz pacing in the absence or presence of EGCg (1.8 µM). At baseline and in the absence of Fura-2, KI cardiomyocytes displayed lower diastolic sarcomere length, higher fractional sarcomere shortening, longer time to peak shortening and time to 50% relengthening than WT cardiomyocytes. In WT and KI neither diastolic sarcomere length nor fractional sarcomere shortening were influenced by EGCg treatment, but relaxation time was reduced, to a greater extent in KI cells. EGCg shortened time to peak Ca2+ and Ca2+ transient decay in Fura-2-loaded WT and KI cardiomyocytes. EGCg did not influence phosphorylation of phospholamban. In skinned cardiac muscle strips, EGCg (30 µM) decreased Ca2+ sensitivity in both groups. Conclusion. EGCg fastened relaxation and Ca2+ transient decay to a larger extent in KI than in WT cardiomyocytes. This effect could be partially explained by myofilament Ca2+ desensitization.http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00607/fullRelaxationHypertrophic Cardiomyopathyepigallocatechin-3-gallateCa2+ transientMyofilament Ca2+ sensitivityMYBPC3 |
| spellingShingle | Felix W. Friedrich Felix W. Friedrich Frederik Flenner Frederik Flenner Mahtab Nasib Mahtab Nasib Thomas Eschenhagen Thomas Eschenhagen Lucie Carrier Lucie Carrier Epigallocatechin-3-gallate accelerates relaxation and Ca2+ transient decay and desensitizes myofilaments in healthy and Mybpc3-targeted knock-in cardiomyopathic mice Frontiers in Physiology Relaxation Hypertrophic Cardiomyopathy epigallocatechin-3-gallate Ca2+ transient Myofilament Ca2+ sensitivity MYBPC3 |
| title | Epigallocatechin-3-gallate accelerates relaxation and Ca2+ transient decay and desensitizes myofilaments in healthy and Mybpc3-targeted knock-in cardiomyopathic mice |
| title_full | Epigallocatechin-3-gallate accelerates relaxation and Ca2+ transient decay and desensitizes myofilaments in healthy and Mybpc3-targeted knock-in cardiomyopathic mice |
| title_fullStr | Epigallocatechin-3-gallate accelerates relaxation and Ca2+ transient decay and desensitizes myofilaments in healthy and Mybpc3-targeted knock-in cardiomyopathic mice |
| title_full_unstemmed | Epigallocatechin-3-gallate accelerates relaxation and Ca2+ transient decay and desensitizes myofilaments in healthy and Mybpc3-targeted knock-in cardiomyopathic mice |
| title_short | Epigallocatechin-3-gallate accelerates relaxation and Ca2+ transient decay and desensitizes myofilaments in healthy and Mybpc3-targeted knock-in cardiomyopathic mice |
| title_sort | epigallocatechin 3 gallate accelerates relaxation and ca2 transient decay and desensitizes myofilaments in healthy and mybpc3 targeted knock in cardiomyopathic mice |
| topic | Relaxation Hypertrophic Cardiomyopathy epigallocatechin-3-gallate Ca2+ transient Myofilament Ca2+ sensitivity MYBPC3 |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00607/full |
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