Description, Staging and Quantification of Pulmonary Artery Angiophagy in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension

Angiophagy has been described as a non-fibrinolytic mechanism of pulmonary artery (PA) patency restoration after distal (<50 µm in diameter) pulmonary embolism in mice. We hypothesized that angiophagy could achieve muscularized PA patency restoration after pulmonary embolism in piglets and humans...

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Main Authors: Frédéric Perros, Maria-Rosa Ghigna, Fanny Loisel, Denis Chemla, Benoit Decante, Vincent de Montpreville, David Montani, Marc Humbert, Elie Fadel, Olaf Mercier, David Boulate
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/8/11/493
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author Frédéric Perros
Maria-Rosa Ghigna
Fanny Loisel
Denis Chemla
Benoit Decante
Vincent de Montpreville
David Montani
Marc Humbert
Elie Fadel
Olaf Mercier
David Boulate
author_facet Frédéric Perros
Maria-Rosa Ghigna
Fanny Loisel
Denis Chemla
Benoit Decante
Vincent de Montpreville
David Montani
Marc Humbert
Elie Fadel
Olaf Mercier
David Boulate
author_sort Frédéric Perros
collection DOAJ
description Angiophagy has been described as a non-fibrinolytic mechanism of pulmonary artery (PA) patency restoration after distal (<50 µm in diameter) pulmonary embolism in mice. We hypothesized that angiophagy could achieve muscularized PA patency restoration after pulmonary embolism in piglets and humans. Angiophagy was defined by pathological assessment as the moving of an embolic specimen from the lumen to the interstitium according to three stages in a pig model of chronic thromboembolic pulmonary hypertension (CTEPH) 6 to 10 weeks after embolization with enbucrilate: the embolic specimen is (I) covered by endothelial cells, (II) covered by endothelial cells and smooth muscle cells, and (III) located in the adventitia. In animals, we observed the three stages of the pulmonary angiophagy of enbucrilate emboli in <300 µm PA. Stages II and III were observed in 300 to 1000 μm PA, and only Stage I was observed in larger-diameter PA (>1000 μm). In lung samples from patients with histories of pulmonary embolisms, we observed PA angiophagy stigma for embolic specimens derived from blood clots and from bone marrow emboli. This study provides an original pathological description and staging of PA angiophagy in a large animal model of CTEPH and in humans after pulmonary embolism.
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spelling doaj.art-e95b0ffc8ad9480fb88455395a3f75842023-11-20T20:32:45ZengMDPI AGBiomedicines2227-90592020-11-0181149310.3390/biomedicines8110493Description, Staging and Quantification of Pulmonary Artery Angiophagy in a Large Animal Model of Chronic Thromboembolic Pulmonary HypertensionFrédéric Perros0Maria-Rosa Ghigna1Fanny Loisel2Denis Chemla3Benoit Decante4Vincent de Montpreville5David Montani6Marc Humbert7Elie Fadel8Olaf Mercier9David Boulate10School of Medicine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceSchool of Medicine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceResearch and Innovation Unit, Hôpital Marie Lannelongue, 92350 Le Plessis-Robinson, FranceSchool of Medicine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceResearch and Innovation Unit, Hôpital Marie Lannelongue, 92350 Le Plessis-Robinson, FranceDepartment of Pathology, Hôpital Marie Lannelongue, 92350 Le Plessis-Robinson, FranceSchool of Medicine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceSchool of Medicine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceSchool of Medicine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceSchool of Medicine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceSchool of Medicine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceAngiophagy has been described as a non-fibrinolytic mechanism of pulmonary artery (PA) patency restoration after distal (<50 µm in diameter) pulmonary embolism in mice. We hypothesized that angiophagy could achieve muscularized PA patency restoration after pulmonary embolism in piglets and humans. Angiophagy was defined by pathological assessment as the moving of an embolic specimen from the lumen to the interstitium according to three stages in a pig model of chronic thromboembolic pulmonary hypertension (CTEPH) 6 to 10 weeks after embolization with enbucrilate: the embolic specimen is (I) covered by endothelial cells, (II) covered by endothelial cells and smooth muscle cells, and (III) located in the adventitia. In animals, we observed the three stages of the pulmonary angiophagy of enbucrilate emboli in <300 µm PA. Stages II and III were observed in 300 to 1000 μm PA, and only Stage I was observed in larger-diameter PA (>1000 μm). In lung samples from patients with histories of pulmonary embolisms, we observed PA angiophagy stigma for embolic specimens derived from blood clots and from bone marrow emboli. This study provides an original pathological description and staging of PA angiophagy in a large animal model of CTEPH and in humans after pulmonary embolism.https://www.mdpi.com/2227-9059/8/11/493pulmonary embolismangiophagypulmonary arteryremodelingpathologyanimal model
spellingShingle Frédéric Perros
Maria-Rosa Ghigna
Fanny Loisel
Denis Chemla
Benoit Decante
Vincent de Montpreville
David Montani
Marc Humbert
Elie Fadel
Olaf Mercier
David Boulate
Description, Staging and Quantification of Pulmonary Artery Angiophagy in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension
Biomedicines
pulmonary embolism
angiophagy
pulmonary artery
remodeling
pathology
animal model
title Description, Staging and Quantification of Pulmonary Artery Angiophagy in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension
title_full Description, Staging and Quantification of Pulmonary Artery Angiophagy in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension
title_fullStr Description, Staging and Quantification of Pulmonary Artery Angiophagy in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension
title_full_unstemmed Description, Staging and Quantification of Pulmonary Artery Angiophagy in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension
title_short Description, Staging and Quantification of Pulmonary Artery Angiophagy in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension
title_sort description staging and quantification of pulmonary artery angiophagy in a large animal model of chronic thromboembolic pulmonary hypertension
topic pulmonary embolism
angiophagy
pulmonary artery
remodeling
pathology
animal model
url https://www.mdpi.com/2227-9059/8/11/493
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