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Macitentan attenuates cardiovascular remodelling in infant rats with chronic lung disease


Baumann, Philipp; Greco, Francesco; Wiegert, Susanne; Wellmann, Sven; Pellegrini, Giovanni; Cannizzaro, Vincenzo (2022). Macitentan attenuates cardiovascular remodelling in infant rats with chronic lung disease. Journal of Translational Medicine, 20(1):77.

Abstract

Background: Cardiovascular impairment contributes to increased mortality in preterm infants with chronic lung disease. Macitentan, an endothelin-1 receptor antagonist, has the potential to attenuate pulmonary and cardiovascular remodelling.
Methods: In a prospective randomized placebo-controlled intervention trial, Sprague–Dawley rats were exposed to 0.21 or 1.0 fraction of inspired oxygen (FiO2) for 19 postnatal days. Rats were treated via gavage with placebo or macitentan from days of life 5 to 19. Alveoli, pulmonary vessels, α-smooth muscle actin content in pulmonary arterioles, size of cardiomyocytes, right to left ventricular wall diameter ratio, and endothelin-1 plasma concentrations were assessed.
Results: FiO2 1.0 induced typical features of chronic lung disease with significant alveolar enlargement (p = 0.012), alveolar (p = 0.048) and pulmonary vessel rarefaction (p = 0.024), higher α-smooth muscle actin content in pulmonary arterioles (p = 0.009), higher right to left ventricular wall diameter ratio (p = 0.02), and larger cardiomyocyte cross-sectional area (p < 0.001). Macitentan treatment significantly increased pulmonary vessel count (p = 0.004) and decreased right to left ventricular wall diameter ratios (p = 0.002). Endothelin-1 plasma concentrations were higher compared to placebo (p = 0.015). Alveolar number and size, α-smooth muscle actin, and the cardiomyocyte cross-sectional area remained unchanged (all p > 0.05).
Conclusion: The endothelin-1 receptor antagonist macitentan attenuated cardiovascular remodelling in an infant rat model for preterm chronic lung disease. This study underscores the potential of macitentan to reduce cardiovascular morbidity in preterm infants with chronic lung disease.

Abstract

Background: Cardiovascular impairment contributes to increased mortality in preterm infants with chronic lung disease. Macitentan, an endothelin-1 receptor antagonist, has the potential to attenuate pulmonary and cardiovascular remodelling.
Methods: In a prospective randomized placebo-controlled intervention trial, Sprague–Dawley rats were exposed to 0.21 or 1.0 fraction of inspired oxygen (FiO2) for 19 postnatal days. Rats were treated via gavage with placebo or macitentan from days of life 5 to 19. Alveoli, pulmonary vessels, α-smooth muscle actin content in pulmonary arterioles, size of cardiomyocytes, right to left ventricular wall diameter ratio, and endothelin-1 plasma concentrations were assessed.
Results: FiO2 1.0 induced typical features of chronic lung disease with significant alveolar enlargement (p = 0.012), alveolar (p = 0.048) and pulmonary vessel rarefaction (p = 0.024), higher α-smooth muscle actin content in pulmonary arterioles (p = 0.009), higher right to left ventricular wall diameter ratio (p = 0.02), and larger cardiomyocyte cross-sectional area (p < 0.001). Macitentan treatment significantly increased pulmonary vessel count (p = 0.004) and decreased right to left ventricular wall diameter ratios (p = 0.002). Endothelin-1 plasma concentrations were higher compared to placebo (p = 0.015). Alveolar number and size, α-smooth muscle actin, and the cardiomyocyte cross-sectional area remained unchanged (all p > 0.05).
Conclusion: The endothelin-1 receptor antagonist macitentan attenuated cardiovascular remodelling in an infant rat model for preterm chronic lung disease. This study underscores the potential of macitentan to reduce cardiovascular morbidity in preterm infants with chronic lung disease.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neonatology
04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Zurich Center for Integrative Human Physiology (ZIHP)
05 Vetsuisse Faculty > Veterinärwissenschaftliches Institut > Institute of Veterinary Pathology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > General Biochemistry, Genetics and Molecular Biology
Uncontrolled Keywords:Bronchopulmonary dysplasia; Chronic lung disease; Endothelin receptor blockers; Infants; Preterm; Rats
Language:English
Date:5 February 2022
Deposited On:06 Apr 2022 13:14
Last Modified:28 May 2024 01:36
Publisher:BioMed Central
ISSN:1479-5876
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s12967-022-03281-2
PubMed ID:35123510
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)