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

PloS One
Eva Amalie NielsenMark K Friedberg

Abstract

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. 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). 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-operate...Continue Reading

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Citations

Mar 22, 2016·International Journal of Molecular Sciences·Xing WangYanjiang Qiao
Dec 7, 2017·Interactive Cardiovascular and Thoracic Surgery·Sara Roldan RamosMark K Friedberg
Sep 29, 2017·Cardiovascular Research·Nikolaos G Frangogiannis
Jun 2, 2018·Circulation. Cardiovascular Imaging·Justin T Tretter, Andrew N Redington
May 21, 2016·American Journal of Physiology. Heart and Circulatory Physiology·P Mendes-FerreiraC Brás-Silva
Jan 9, 2019·Frontiers in Cardiovascular Medicine·Gayathri ViswanathanSudarshan Rajagopal
Apr 18, 2019·Journal of Human Hypertension·Andrea Maria MarescaLuigina Guasti
Sep 12, 2020·American Journal of Respiratory Cell and Molecular Biology·Ryo IshiiMark K Friedberg

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Methods Mentioned

BETA
blood
PCR
unbiquitination

Software Mentioned

GraphPad Prism
NIH ImageJ
Adobe Photoshop

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