Enhanced myofilament responsiveness upon β-adrenergic stimulation in post-infarct remodeled myocardium

Nicky M Boontje; Daphne Merkus; Ruud Zaremba; Amanda Versteilen; de Waard; Giulia Mearini; Giulia Mearini; Lucie Carrier; J Vincent; Lucie Carrier; Lori A Walker; Hans W M Niessen; Dobromir Dobrev; Ger J M Stienen; Dirk J Duncker; Jolanda van der Velden

doi:10.1016/j.yjmcc.2010.12.002

Enhanced myofilament responsiveness upon β-adrenergic stimulation in post-infarct remodeled myocardium

Standard

Enhanced myofilament responsiveness upon β-adrenergic stimulation in post-infarct remodeled myocardium. / Boontje, Nicky M; Merkus, Daphne; Zaremba, Ruud; Versteilen, Amanda; Waard, de; Mearini, Giulia; Mearini, Giulia; Carrier, Lucie; Vincent, J; Carrier, Lucie; Walker, Lori A; Niessen, Hans W M; Dobrev, Dobromir; Stienen, Ger J M; Duncker, Dirk J; van der Velden, Jolanda.

in: J MOL CELL CARDIOL, Jahrgang 50, Nr. 3, 3, 01.03.2011, S. 487-499.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Boontje, NM, Merkus, D, Zaremba, R, Versteilen, A, Waard, D, Mearini, G, Mearini, G, Carrier, L, Vincent, J, Carrier, L, Walker, LA, Niessen, HWM, Dobrev, D, Stienen, GJM, Duncker, DJ & van der Velden, J 2011, 'Enhanced myofilament responsiveness upon β-adrenergic stimulation in post-infarct remodeled myocardium', J MOL CELL CARDIOL, Jg. 50, Nr. 3, 3, S. 487-499. https://doi.org/10.1016/j.yjmcc.2010.12.002

APA

Boontje, N. M., Merkus, D., Zaremba, R., Versteilen, A., Waard, D., Mearini, G., Mearini, G., Carrier, L., Vincent, J., Carrier, L., Walker, L. A., Niessen, H. W. M., Dobrev, D., Stienen, G. J. M., Duncker, D. J., & van der Velden, J. (2011). Enhanced myofilament responsiveness upon β-adrenergic stimulation in post-infarct remodeled myocardium. J MOL CELL CARDIOL, 50(3), 487-499. [3]. https://doi.org/10.1016/j.yjmcc.2010.12.002

Vancouver

Boontje NM, Merkus D, Zaremba R, Versteilen A, Waard D, Mearini G et al. Enhanced myofilament responsiveness upon β-adrenergic stimulation in post-infarct remodeled myocardium. J MOL CELL CARDIOL. 2011 Mär 1;50(3):487-499. 3. https://doi.org/10.1016/j.yjmcc.2010.12.002

Bibtex

@article{fef3beb25986487dbe43d66008becfc4,

title = "Enhanced myofilament responsiveness upon β-adrenergic stimulation in post-infarct remodeled myocardium",

abstract = "Previously we showed that left ventricular (LV) responsiveness to exercise-induced increases in noradrenaline was blunted in pigs with a recent myocardial infarction (MI) [van der Velden et al. Circ Res. 2004], consistent with perturbed -adrenergic receptor ( -AR) signaling. Here we tested the hypothesis that abnormalities at the myofilament level underlie impaired LV responsiveness to catecholamines in MI. Myofilament function and protein composition were studied in remote LV biopsies taken at baseline and during dobutamine stimulation 3 weeks after MI or sham. Single permeabilized cardiomyocytes demonstrated reduced maximal force (F(max)) and higher Ca(2+)-sensitivity in MI compared to sham. F(max) did not change during dobutamine infusion in sham, but markedly increased in MI. Moreover, the dobutamine-induced decrease in Ca(2+)-sensitivity was significantly larger in MI than sham. Baseline phosphorylation assessed by phosphostaining of -AR target proteins myosin binding protein C (cMyBP-C) and troponin I (cTnI) in MI and sham was the same. However, the dobutamine-induced increase in overall cTnI phosphorylation and cTnI phosphorylation at protein kinase A (PKA)-sites (Ser23/24) was less in MI compared to sham. In contrast, the dobutamine-induced phosphorylation of cMyBP-C at Ser282 was preserved in MI, and coincided with increased autophosphorylation (at Thr282) of the cytosolic Ca(2+)-dependent calmodulin kinase II (CaMKII- C). In conclusion, in post-infarct remodeled myocardium myofilament responsiveness to dobutamine is significantly enhanced despite the lower increase in PKA-mediated phosphorylation of cTnI. The increased myofilament responsiveness in MI may depend on the preserved cMyBP-C phosphorylation possibly resulting from increased CaMKII- C activity and may help to maintain proper diastolic performance during exercise.",

keywords = "Actin Cytoskeleton, Adrenergic beta-1 Receptor Agonists, Animals, Calcium, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Carrier Proteins, Catecholamines, Cyclic AMP-Dependent Protein Kinases, Dobutamine, Female, Heart Ventricles, Male, Myocardial Infarction, Myocardium, Myocytes, Cardiac, Phosphorylation, Receptors, Adrenergic, beta, Swine, Troponin I, Ventricular Remodeling",

author = "Boontje, {Nicky M} and Daphne Merkus and Ruud Zaremba and Amanda Versteilen and de Waard and Giulia Mearini and Giulia Mearini and Lucie Carrier and J Vincent and Lucie Carrier and Walker, {Lori A} and Niessen, {Hans W M} and Dobromir Dobrev and Stienen, {Ger J M} and Duncker, {Dirk J} and {van der Velden}, Jolanda",

year = "2011",

month = mar,

day = "1",

doi = "10.1016/j.yjmcc.2010.12.002",

language = "English",

volume = "50",

pages = "487--499",

journal = "J MOL CELL CARDIOL",

issn = "0022-2828",

publisher = "Academic Press Inc.",

number = "3",

}

RIS

TY - JOUR

T1 - Enhanced myofilament responsiveness upon β-adrenergic stimulation in post-infarct remodeled myocardium

AU - Boontje, Nicky M

AU - Merkus, Daphne

AU - Zaremba, Ruud

AU - Versteilen, Amanda

AU - Waard, de

AU - Mearini, Giulia

AU - Carrier, Lucie

AU - Vincent, J

AU - Carrier, Lucie

AU - Walker, Lori A

AU - Niessen, Hans W M

AU - Dobrev, Dobromir

AU - Stienen, Ger J M

AU - Duncker, Dirk J

AU - van der Velden, Jolanda

PY - 2011/3/1

Y1 - 2011/3/1

N2 - Previously we showed that left ventricular (LV) responsiveness to exercise-induced increases in noradrenaline was blunted in pigs with a recent myocardial infarction (MI) [van der Velden et al. Circ Res. 2004], consistent with perturbed -adrenergic receptor ( -AR) signaling. Here we tested the hypothesis that abnormalities at the myofilament level underlie impaired LV responsiveness to catecholamines in MI. Myofilament function and protein composition were studied in remote LV biopsies taken at baseline and during dobutamine stimulation 3 weeks after MI or sham. Single permeabilized cardiomyocytes demonstrated reduced maximal force (F(max)) and higher Ca(2+)-sensitivity in MI compared to sham. F(max) did not change during dobutamine infusion in sham, but markedly increased in MI. Moreover, the dobutamine-induced decrease in Ca(2+)-sensitivity was significantly larger in MI than sham. Baseline phosphorylation assessed by phosphostaining of -AR target proteins myosin binding protein C (cMyBP-C) and troponin I (cTnI) in MI and sham was the same. However, the dobutamine-induced increase in overall cTnI phosphorylation and cTnI phosphorylation at protein kinase A (PKA)-sites (Ser23/24) was less in MI compared to sham. In contrast, the dobutamine-induced phosphorylation of cMyBP-C at Ser282 was preserved in MI, and coincided with increased autophosphorylation (at Thr282) of the cytosolic Ca(2+)-dependent calmodulin kinase II (CaMKII- C). In conclusion, in post-infarct remodeled myocardium myofilament responsiveness to dobutamine is significantly enhanced despite the lower increase in PKA-mediated phosphorylation of cTnI. The increased myofilament responsiveness in MI may depend on the preserved cMyBP-C phosphorylation possibly resulting from increased CaMKII- C activity and may help to maintain proper diastolic performance during exercise.

AB - Previously we showed that left ventricular (LV) responsiveness to exercise-induced increases in noradrenaline was blunted in pigs with a recent myocardial infarction (MI) [van der Velden et al. Circ Res. 2004], consistent with perturbed -adrenergic receptor ( -AR) signaling. Here we tested the hypothesis that abnormalities at the myofilament level underlie impaired LV responsiveness to catecholamines in MI. Myofilament function and protein composition were studied in remote LV biopsies taken at baseline and during dobutamine stimulation 3 weeks after MI or sham. Single permeabilized cardiomyocytes demonstrated reduced maximal force (F(max)) and higher Ca(2+)-sensitivity in MI compared to sham. F(max) did not change during dobutamine infusion in sham, but markedly increased in MI. Moreover, the dobutamine-induced decrease in Ca(2+)-sensitivity was significantly larger in MI than sham. Baseline phosphorylation assessed by phosphostaining of -AR target proteins myosin binding protein C (cMyBP-C) and troponin I (cTnI) in MI and sham was the same. However, the dobutamine-induced increase in overall cTnI phosphorylation and cTnI phosphorylation at protein kinase A (PKA)-sites (Ser23/24) was less in MI compared to sham. In contrast, the dobutamine-induced phosphorylation of cMyBP-C at Ser282 was preserved in MI, and coincided with increased autophosphorylation (at Thr282) of the cytosolic Ca(2+)-dependent calmodulin kinase II (CaMKII- C). In conclusion, in post-infarct remodeled myocardium myofilament responsiveness to dobutamine is significantly enhanced despite the lower increase in PKA-mediated phosphorylation of cTnI. The increased myofilament responsiveness in MI may depend on the preserved cMyBP-C phosphorylation possibly resulting from increased CaMKII- C activity and may help to maintain proper diastolic performance during exercise.

KW - Actin Cytoskeleton

KW - Adrenergic beta-1 Receptor Agonists

KW - Animals

KW - Calcium

KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2

KW - Carrier Proteins

KW - Catecholamines

KW - Cyclic AMP-Dependent Protein Kinases

KW - Dobutamine

KW - Female

KW - Heart Ventricles

KW - Male

KW - Myocardial Infarction

KW - Myocardium

KW - Myocytes, Cardiac

KW - Phosphorylation

KW - Receptors, Adrenergic, beta

KW - Swine

KW - Troponin I

KW - Ventricular Remodeling

U2 - 10.1016/j.yjmcc.2010.12.002

DO - 10.1016/j.yjmcc.2010.12.002

M3 - SCORING: Journal article

C2 - 21156182

VL - 50

SP - 487

EP - 499

JO - J MOL CELL CARDIOL

JF - J MOL CELL CARDIOL

SN - 0022-2828

IS - 3

M1 - 3

ER -