Selective improvement of pulmonary arterial hypertension with a dual ETA/ETB receptors antagonist in the apolipoprotein E−/− model of PAH and atherosclerosis

PVRI Member Authors: Allan Lawrie

Abstract

Idiopathic pulmonary arterial hypertension (IPAH) is increasingly diagnosed in elderly patients who also have an increased risk of co-morbid atherosclerosis. Apolipoprotein E-deficient (ApoE−/−) mice develop atherosclerosis with severe PAH when fed a high-fat diet (HFD) and have increased levels of endothelin (ET)-1. ET-1 receptor antagonists (ERAs) are used for the treatment of PAH but less is known about whether ERAs are beneficial in atherosclerosis. We therefore examined whether treatment of HFD-ApoE−/− mice with macitentan, a dual ETA/ETB receptor antagonist, would have any effect on both atherosclerosis and PAH. ApoE−/− mice were fed chow or HFD for eight weeks. After four weeks of HFD, mice were randomized to a four-week treatment of macitentan by food (30 mg/kg/day dual ETA/ETB antagonist), or placebo groups. Echocardiography and closed-chest right heart catheterization were used to determine PAH phenotype and serum samples were collected for cytokine analysis. . . . .

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Topics

Endothelin and Endothelium & Epithelium and Epithelial Transport
Pulmonary Arterial Hypertension
Pulmonary Hypertension

Authors

Lewis Renshall, Nadine Arnold, Laura West, Adam Braithwaite, Josephine Pickworth, Rachel Walker, Mabruka Alfaidi, Janet Chamberlain, Helen Casbolt, A.A. Roger Thompson, Cathy Holt, Marc Iglarz, Sheila Francis

Published in:

Pulmonary Circulation Vol 8: No 1 cover image

March 2018

Pulmonary Circulation Vol 8: No 1

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