Exploring the Endothelin-1 pathway in chronic thromboembolic pulmonary hypertension microvasculopathy.
Autor: | Feriel B; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France., Alessandra C; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France., Deborah GJ; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France., Corinne N; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France., Raphaël T; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France., Mina O; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France., Ali A; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France.; Department of Thoracic Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital -Groupe Hospitalier Paris Saint Joseph, Le Plessis-Robinson, France., Jean-Baptiste M; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France.; Department of Thoracic Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital -Groupe Hospitalier Paris Saint Joseph, Le Plessis-Robinson, France., Guillaume F; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France.; Department of Thoracic Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital -Groupe Hospitalier Paris Saint Joseph, Le Plessis-Robinson, France., Julien G; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France., Maria-Rosa G; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France., Elie F; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France.; Department of Thoracic Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital -Groupe Hospitalier Paris Saint Joseph, Le Plessis-Robinson, France., Laurent S; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France.; Department of Respiratory and Intensive Care Medicine, Assistance Publique - Hôpitaux de Paris (AP-HP), Pulmonary Hypertension National Referral Center, Bicêtre Hospital, Le Kremlin-Bicêtre, France., Olaf M; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France.; Department of Respiratory and Intensive Care Medicine, Assistance Publique - Hôpitaux de Paris (AP-HP), Pulmonary Hypertension National Referral Center, Bicêtre Hospital, Le Kremlin-Bicêtre, France., Ly T; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France., Marc H; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France.; Department of Respiratory and Intensive Care Medicine, Assistance Publique - Hôpitaux de Paris (AP-HP), Pulmonary Hypertension National Referral Center, Bicêtre Hospital, Le Kremlin-Bicêtre, France., Christophe G; UMR_S 999 'Pulmonary Hypertension: Pathophysiology and Novel Therapies' (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France. christophe.guignabert@inserm.fr.; School of Medicine, University of Paris-Saclay, HPPIT, Le Kremlin-Bicêtre, France. christophe.guignabert@inserm.fr. |
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Jazyk: | angličtina |
Zdroj: | Scientific reports [Sci Rep] 2024 Nov 16; Vol. 14 (1), pp. 28308. Date of Electronic Publication: 2024 Nov 16. |
DOI: | 10.1038/s41598-024-79623-5 |
Abstrakt: | Targeted vasopeptide therapies have significantly advanced the management of pulmonary arterial hypertension (PAH). However, due to insufficient preclinical evidence regarding the involvement of the endothelin-1 (ET-1) pathway in chronic thromboembolic pulmonary hypertension (CTEPH) pathophysiology, the potential of ET-1 receptor antagonism in treating CTEPH remains uncertain. In this study, we investigated the role of the ET-1 pathway in CTEPH microvasculopathy using a multifaceted approach. Plasma ET-1 levels were measured in a cohort of 59 CTEPH patients and 41 healthy controls. Additionally, we evaluated the expression of key ET-1 pathway members in pulmonary explants from CTEPH, idiopathic PAH, and control patients. We used an in vitro system to test the hypothesis that the turbulent flow, observed near the vascular obstructions pathognomonic of CTEPH, enhances ET-1 expression. Our findings were further validated in vivo using a CTEPH piglet model that contains distinct regions representing pre- and post-thrombus lung territories. We found a twofold increase in circulating ET-1 levels in CTEPH patients compared to healthy subjects. Pulmonary explants from CTEPH patients exhibited pronounced overexpression of ET-1, endothelin receptor A (ET Competing Interests: Declarations Competing interests Over the last three years, C.G. reports grants from Acceleron Pharma (Cambridge, MA, USA), a wholly-owned subsidiary of Merck & Co., Inc. (Rahway, NJ, USA), MSD, Corteria, Structure therapeutics, Diagonal Therapeutics, Gossamer, outside the submitted work. M.H. reports grants and personal fees from Acceleron, Aerovate, Altavant, AOP Orphan, Bayer, Chiesi, Ferrer, Janssen, Merck, MorphogenIX and United Therapeutics, outside the submitted work. All the other authors declare that there is no conflict of interest regarding the publication of this original article. (© 2024. The Author(s).) |
Databáze: | MEDLINE |
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