Dual ETA/ETB blockade with macitentan improves both vascular remodeling and angiogenesis in pulmonary arterial hypertension

PVRI Member Authors: Steeve Provencher, Dr. Olivier Boucherat, Sebastien Bonnet, Christopher Plowman, Francois Potus

Abstract

Dysregulated metabolism and rarefaction of the capillary network play a critical role in pulmonary arterial hypertension (PAH) etiology. They are associated with a decrease in perfusion of the lungs, skeletal muscles, and right ventricle (RV). Previous studies suggested that endothelin-1 (ET-1) modulates both metabolism and angiogenesis. We hypothesized that dual ETA/ETB receptors blockade improves PAH by improving cell metabolism and promoting angiogenesis. Five weeks after disease induction, Sugen/hypoxic rats presented severe PAH with pulmonary artery (PA) remodeling, RV hypertrophy and capillary rarefaction in the lungs, RV, and skeletal muscles (microCT angiogram, lectin perfusion, CD31 staining). Two-week treatment with dual ETA/ETB receptors antagonist macitentan (30 mg/kg/d) significantly improved pulmonary hemodynamics, PA vascular remodeling, and RV function and hypertrophy compared to vehicle-treated animals (all P = 0.05). . . . .

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Topics

Endothelin and Endothelium & Epithelium and Epithelial Transport
Pulmonary Hypertension
Pulmonary Vascular Remodeling

Authors

Valerie Nadeau, Renee Paradis, Eve Tremblay, Marc Iglarz, Roxane Paulin

Published in:

Pulmonary Circulation Vol 8: No 1 cover image

March 2018

Pulmonary Circulation Vol 8: No 1

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