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CNP regulates cardiac contractility and increases cGMP near both SERCA and TnI - difference from BNP visualized by targeted cGMP biosensors

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CNP regulates cardiac contractility and increases cGMP near both SERCA and TnI - difference from BNP visualized by targeted cGMP biosensors. / Manfra, Ornella; Calamera, Gaia; Froese, Alexander; Arunthavarajah, Dulasi; Surdo, Nicoletta C; Meier, Silja; Melleby, Arne Olav; Aasrum, Monica; Aronsen, Jan Magnus; Nikolaev, Viacheslav O; Zaccolo, Manuela; Moltzau, Lise Román; Levy, Finn Olav; Andressen, Kjetil Wessel.

In: CARDIOVASC RES, Vol. 118, No. 6, 06.05.2022, p. 1506-1519.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Manfra, O, Calamera, G, Froese, A, Arunthavarajah, D, Surdo, NC, Meier, S, Melleby, AO, Aasrum, M, Aronsen, JM, Nikolaev, VO, Zaccolo, M, Moltzau, LR, Levy, FO & Andressen, KW 2022, 'CNP regulates cardiac contractility and increases cGMP near both SERCA and TnI - difference from BNP visualized by targeted cGMP biosensors', CARDIOVASC RES, vol. 118, no. 6, pp. 1506-1519. https://doi.org/10.1093/cvr/cvab167

APA

Manfra, O., Calamera, G., Froese, A., Arunthavarajah, D., Surdo, N. C., Meier, S., Melleby, A. O., Aasrum, M., Aronsen, J. M., Nikolaev, V. O., Zaccolo, M., Moltzau, L. R., Levy, F. O., & Andressen, K. W. (2022). CNP regulates cardiac contractility and increases cGMP near both SERCA and TnI - difference from BNP visualized by targeted cGMP biosensors. CARDIOVASC RES, 118(6), 1506-1519. https://doi.org/10.1093/cvr/cvab167

Vancouver

Manfra O, Calamera G, Froese A, Arunthavarajah D, Surdo NC, Meier S et al. CNP regulates cardiac contractility and increases cGMP near both SERCA and TnI - difference from BNP visualized by targeted cGMP biosensors. CARDIOVASC RES. 2022 May 6;118(6):1506-1519. https://doi.org/10.1093/cvr/cvab167

Bibtex

@article{0e4f53ec2e284b60bd43e7e2717fe714,
title = "CNP regulates cardiac contractility and increases cGMP near both SERCA and TnI - difference from BNP visualized by targeted cGMP biosensors",
abstract = "AIMS: Guanylyl cyclase-B (GC-B; natriuretic peptide receptor-B, NPR-B) stimulation by C-type natriuretic peptide (CNP) increases cGMP and causes a lusitropic and negative inotropic response in adult myocardium. These effects are not mimicked by NPR-A (GC-A) stimulation by brain natriuretic peptide (BNP), despite similar cGMP increase. More refined methods are needed to better understand the mechanisms of the differential cGMP signalling and compartmentation. The aim of this work was to measure cGMP near proteins involved in regulating contractility to understand compartmentation of cGMP signalling in adult cardiomyocytes.METHODS AND RESULTS: We constructed several fluorescence resonance energy transfer (FRET)-based biosensors for cGMP subcellularly targeted to phospholamban (PLB) and troponin I (TnI). CNP stimulation of adult rat cardiomyocytes increased cGMP near PLB and TnI, whereas BNP stimulation increased cGMP near PLB, but not TnI. The phosphodiesterases PDE2 and PDE3 constrained cGMP in both compartments. Local receptor stimulation aided by scanning ion conductance microscopy (SICM) combined with FRET revealed that CNP stimulation both in the t-tubules and on the cell crest increases cGMP similarly near both TnI and PLB. In ventricular strips, CNP stimulation, but not BNP, induced a lusitropic response, enhanced by inhibition of either PDE2 or PDE3, and a negative inotropic response. In cardiomyocytes from heart failure rats, CNP increased cGMP near PLB and TnI more pronounced than in cells from sham-operated animals.CONCLUSION: These targeted biosensors demonstrate that CNP, but not BNP, increases cGMP near TnI in addition to PLB, explaining how CNP, but not BNP, is able to induce lusitropic and negative inotropic responses.",
author = "Ornella Manfra and Gaia Calamera and Alexander Froese and Dulasi Arunthavarajah and Surdo, {Nicoletta C} and Silja Meier and Melleby, {Arne Olav} and Monica Aasrum and Aronsen, {Jan Magnus} and Nikolaev, {Viacheslav O} and Manuela Zaccolo and Moltzau, {Lise Rom{\'a}n} and Levy, {Finn Olav} and Andressen, {Kjetil Wessel}",
note = "{\textcopyright} The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.",
year = "2022",
month = may,
day = "6",
doi = "10.1093/cvr/cvab167",
language = "English",
volume = "118",
pages = "1506--1519",
journal = "CARDIOVASC RES",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "6",

}

RIS

TY - JOUR

T1 - CNP regulates cardiac contractility and increases cGMP near both SERCA and TnI - difference from BNP visualized by targeted cGMP biosensors

AU - Manfra, Ornella

AU - Calamera, Gaia

AU - Froese, Alexander

AU - Arunthavarajah, Dulasi

AU - Surdo, Nicoletta C

AU - Meier, Silja

AU - Melleby, Arne Olav

AU - Aasrum, Monica

AU - Aronsen, Jan Magnus

AU - Nikolaev, Viacheslav O

AU - Zaccolo, Manuela

AU - Moltzau, Lise Román

AU - Levy, Finn Olav

AU - Andressen, Kjetil Wessel

N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

PY - 2022/5/6

Y1 - 2022/5/6

N2 - AIMS: Guanylyl cyclase-B (GC-B; natriuretic peptide receptor-B, NPR-B) stimulation by C-type natriuretic peptide (CNP) increases cGMP and causes a lusitropic and negative inotropic response in adult myocardium. These effects are not mimicked by NPR-A (GC-A) stimulation by brain natriuretic peptide (BNP), despite similar cGMP increase. More refined methods are needed to better understand the mechanisms of the differential cGMP signalling and compartmentation. The aim of this work was to measure cGMP near proteins involved in regulating contractility to understand compartmentation of cGMP signalling in adult cardiomyocytes.METHODS AND RESULTS: We constructed several fluorescence resonance energy transfer (FRET)-based biosensors for cGMP subcellularly targeted to phospholamban (PLB) and troponin I (TnI). CNP stimulation of adult rat cardiomyocytes increased cGMP near PLB and TnI, whereas BNP stimulation increased cGMP near PLB, but not TnI. The phosphodiesterases PDE2 and PDE3 constrained cGMP in both compartments. Local receptor stimulation aided by scanning ion conductance microscopy (SICM) combined with FRET revealed that CNP stimulation both in the t-tubules and on the cell crest increases cGMP similarly near both TnI and PLB. In ventricular strips, CNP stimulation, but not BNP, induced a lusitropic response, enhanced by inhibition of either PDE2 or PDE3, and a negative inotropic response. In cardiomyocytes from heart failure rats, CNP increased cGMP near PLB and TnI more pronounced than in cells from sham-operated animals.CONCLUSION: These targeted biosensors demonstrate that CNP, but not BNP, increases cGMP near TnI in addition to PLB, explaining how CNP, but not BNP, is able to induce lusitropic and negative inotropic responses.

AB - AIMS: Guanylyl cyclase-B (GC-B; natriuretic peptide receptor-B, NPR-B) stimulation by C-type natriuretic peptide (CNP) increases cGMP and causes a lusitropic and negative inotropic response in adult myocardium. These effects are not mimicked by NPR-A (GC-A) stimulation by brain natriuretic peptide (BNP), despite similar cGMP increase. More refined methods are needed to better understand the mechanisms of the differential cGMP signalling and compartmentation. The aim of this work was to measure cGMP near proteins involved in regulating contractility to understand compartmentation of cGMP signalling in adult cardiomyocytes.METHODS AND RESULTS: We constructed several fluorescence resonance energy transfer (FRET)-based biosensors for cGMP subcellularly targeted to phospholamban (PLB) and troponin I (TnI). CNP stimulation of adult rat cardiomyocytes increased cGMP near PLB and TnI, whereas BNP stimulation increased cGMP near PLB, but not TnI. The phosphodiesterases PDE2 and PDE3 constrained cGMP in both compartments. Local receptor stimulation aided by scanning ion conductance microscopy (SICM) combined with FRET revealed that CNP stimulation both in the t-tubules and on the cell crest increases cGMP similarly near both TnI and PLB. In ventricular strips, CNP stimulation, but not BNP, induced a lusitropic response, enhanced by inhibition of either PDE2 or PDE3, and a negative inotropic response. In cardiomyocytes from heart failure rats, CNP increased cGMP near PLB and TnI more pronounced than in cells from sham-operated animals.CONCLUSION: These targeted biosensors demonstrate that CNP, but not BNP, increases cGMP near TnI in addition to PLB, explaining how CNP, but not BNP, is able to induce lusitropic and negative inotropic responses.

U2 - 10.1093/cvr/cvab167

DO - 10.1093/cvr/cvab167

M3 - SCORING: Journal article

C2 - 33970224

VL - 118

SP - 1506

EP - 1519

JO - CARDIOVASC RES

JF - CARDIOVASC RES

SN - 0008-6363

IS - 6

ER -