Dual Endothelin Receptor Blockade Abrogates Right Ventricular Remodeling and Biventricular Fibrosis in Isolated Elevated Right Ventricular Afterload

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Standard

Dual Endothelin Receptor Blockade Abrogates Right Ventricular Remodeling and Biventricular Fibrosis in Isolated Elevated Right Ventricular Afterload. / Nielsen, Eva Amalie; Sun, Mei; Honjo, Osami; Hjortdal, Vibeke E; Redington, Andrew N; Friedberg, Mark K.

I: PLoS ONE, Bind 11, Nr. 1, 2016, s. e0146767.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Nielsen, EA, Sun, M, Honjo, O, Hjortdal, VE, Redington, AN & Friedberg, MK 2016, 'Dual Endothelin Receptor Blockade Abrogates Right Ventricular Remodeling and Biventricular Fibrosis in Isolated Elevated Right Ventricular Afterload', PLoS ONE, bind 11, nr. 1, s. e0146767. https://doi.org/10.1371/journal.pone.0146767

APA

Nielsen, E. A., Sun, M., Honjo, O., Hjortdal, V. E., Redington, A. N., & Friedberg, M. K. (2016). Dual Endothelin Receptor Blockade Abrogates Right Ventricular Remodeling and Biventricular Fibrosis in Isolated Elevated Right Ventricular Afterload. PLoS ONE, 11(1), e0146767. https://doi.org/10.1371/journal.pone.0146767

Vancouver

Nielsen EA, Sun M, Honjo O, Hjortdal VE, Redington AN, Friedberg MK. Dual Endothelin Receptor Blockade Abrogates Right Ventricular Remodeling and Biventricular Fibrosis in Isolated Elevated Right Ventricular Afterload. PLoS ONE. 2016;11(1):e0146767. https://doi.org/10.1371/journal.pone.0146767

Author

Nielsen, Eva Amalie ; Sun, Mei ; Honjo, Osami ; Hjortdal, Vibeke E ; Redington, Andrew N ; Friedberg, Mark K. / Dual Endothelin Receptor Blockade Abrogates Right Ventricular Remodeling and Biventricular Fibrosis in Isolated Elevated Right Ventricular Afterload. I: PLoS ONE. 2016 ; Bind 11, Nr. 1. s. e0146767.

Bibtex

@article{e2fd514747b94ea983c0db03356457fc,
title = "Dual Endothelin Receptor Blockade Abrogates Right Ventricular Remodeling and Biventricular Fibrosis in Isolated Elevated Right Ventricular Afterload",
abstract = "BACKGROUND: Pulmonary arterial hypertension is usually fatal due to right ventricular failure and is frequently associated with co-existing left ventricular dysfunction. Endothelin-1 is a powerful pro-fibrotic mediator and vasoconstrictor that is elevated in pulmonary arterial hypertension. Endothelin receptor blockers are commonly used as pulmonary vasodilators, however their effect on biventricular injury, remodeling and function, despite elevated isolated right ventricular afterload is unknown.METHODS: Elevated right ventricular afterload was induced by progressive pulmonary artery banding. Seven rabbits underwent pulmonary artery banding without macitentan; 13 received pulmonary artery banding + macitentan; and 5 did not undergo inflation of the pulmonary artery band (sham-operated controls).RESULTS: Right and left ventricular collagen content was increased with pulmonary artery banding compared to sham-operated controls and ameliorated by macitentan. Right ventricular fibrosis signaling (connective tissue growth factor and endothelin-1 protein levels); extra-cellular matrix remodeling (matrix-metalloproteinases 2 and 9), apoptosis and apoptosis-related peptides (caspases 3 and 8) were increased with pulmonary artery banding compared with sham-operated controls and decreased with macitentan.CONCLUSION: Isolated right ventricular afterload causes biventricular fibrosis, right ventricular apoptosis and extra cellular matrix remodeling, mediated by up-regulation of endothelin-1 and connective tissue growth factor signaling. These pathological changes are ameliorated by dual endothelin receptor blockade despite persistent elevated right ventricular afterload.",
keywords = "Animals, Apoptosis, Disease Models, Animal, Echocardiography, Endothelin-1/blood, Extracellular Matrix/metabolism, Fibrosis, Gene Expression, Heart Ventricles/drug effects, Hemodynamics, Hypertension, Pulmonary/metabolism, Male, Matrix Metalloproteinase 2/metabolism, Matrix Metalloproteinase 9/metabolism, Pyrimidines/blood, RNA, Messenger/genetics, Rabbits, Receptors, Endothelin/metabolism, Signal Transduction, Sulfonamides/blood, Ventricular Dysfunction, Right, Ventricular Remodeling/drug effects",
author = "Nielsen, {Eva Amalie} and Mei Sun and Osami Honjo and Hjortdal, {Vibeke E} and Redington, {Andrew N} and Friedberg, {Mark K}",
year = "2016",
doi = "10.1371/journal.pone.0146767",
language = "English",
volume = "11",
pages = "e0146767",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

RIS

TY - JOUR

T1 - Dual Endothelin Receptor Blockade Abrogates Right Ventricular Remodeling and Biventricular Fibrosis in Isolated Elevated Right Ventricular Afterload

AU - Nielsen, Eva Amalie

AU - Sun, Mei

AU - Honjo, Osami

AU - Hjortdal, Vibeke E

AU - Redington, Andrew N

AU - Friedberg, Mark K

PY - 2016

Y1 - 2016

N2 - BACKGROUND: Pulmonary arterial hypertension is usually fatal due to right ventricular failure and is frequently associated with co-existing left ventricular dysfunction. Endothelin-1 is a powerful pro-fibrotic mediator and vasoconstrictor that is elevated in pulmonary arterial hypertension. Endothelin receptor blockers are commonly used as pulmonary vasodilators, however their effect on biventricular injury, remodeling and function, despite elevated isolated right ventricular afterload is unknown.METHODS: Elevated right ventricular afterload was induced by progressive pulmonary artery banding. Seven rabbits underwent pulmonary artery banding without macitentan; 13 received pulmonary artery banding + macitentan; and 5 did not undergo inflation of the pulmonary artery band (sham-operated controls).RESULTS: Right and left ventricular collagen content was increased with pulmonary artery banding compared to sham-operated controls and ameliorated by macitentan. Right ventricular fibrosis signaling (connective tissue growth factor and endothelin-1 protein levels); extra-cellular matrix remodeling (matrix-metalloproteinases 2 and 9), apoptosis and apoptosis-related peptides (caspases 3 and 8) were increased with pulmonary artery banding compared with sham-operated controls and decreased with macitentan.CONCLUSION: Isolated right ventricular afterload causes biventricular fibrosis, right ventricular apoptosis and extra cellular matrix remodeling, mediated by up-regulation of endothelin-1 and connective tissue growth factor signaling. These pathological changes are ameliorated by dual endothelin receptor blockade despite persistent elevated right ventricular afterload.

AB - BACKGROUND: Pulmonary arterial hypertension is usually fatal due to right ventricular failure and is frequently associated with co-existing left ventricular dysfunction. Endothelin-1 is a powerful pro-fibrotic mediator and vasoconstrictor that is elevated in pulmonary arterial hypertension. Endothelin receptor blockers are commonly used as pulmonary vasodilators, however their effect on biventricular injury, remodeling and function, despite elevated isolated right ventricular afterload is unknown.METHODS: Elevated right ventricular afterload was induced by progressive pulmonary artery banding. Seven rabbits underwent pulmonary artery banding without macitentan; 13 received pulmonary artery banding + macitentan; and 5 did not undergo inflation of the pulmonary artery band (sham-operated controls).RESULTS: Right and left ventricular collagen content was increased with pulmonary artery banding compared to sham-operated controls and ameliorated by macitentan. Right ventricular fibrosis signaling (connective tissue growth factor and endothelin-1 protein levels); extra-cellular matrix remodeling (matrix-metalloproteinases 2 and 9), apoptosis and apoptosis-related peptides (caspases 3 and 8) were increased with pulmonary artery banding compared with sham-operated controls and decreased with macitentan.CONCLUSION: Isolated right ventricular afterload causes biventricular fibrosis, right ventricular apoptosis and extra cellular matrix remodeling, mediated by up-regulation of endothelin-1 and connective tissue growth factor signaling. These pathological changes are ameliorated by dual endothelin receptor blockade despite persistent elevated right ventricular afterload.

KW - Animals

KW - Apoptosis

KW - Disease Models, Animal

KW - Echocardiography

KW - Endothelin-1/blood

KW - Extracellular Matrix/metabolism

KW - Fibrosis

KW - Gene Expression

KW - Heart Ventricles/drug effects

KW - Hemodynamics

KW - Hypertension, Pulmonary/metabolism

KW - Male

KW - Matrix Metalloproteinase 2/metabolism

KW - Matrix Metalloproteinase 9/metabolism

KW - Pyrimidines/blood

KW - RNA, Messenger/genetics

KW - Rabbits

KW - Receptors, Endothelin/metabolism

KW - Signal Transduction

KW - Sulfonamides/blood

KW - Ventricular Dysfunction, Right

KW - Ventricular Remodeling/drug effects

U2 - 10.1371/journal.pone.0146767

DO - 10.1371/journal.pone.0146767

M3 - Journal article

C2 - 26765263

VL - 11

SP - e0146767

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 1

ER -

ID: 242413029