Angiopoietin 2 and hsCRP are associated with pulmonary hemodynamics and long-term mortality respectively in CTEPH-Results from a prospective discovery and validation biomarker study
Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved..
INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed disease of uncertain etiology. Altered endothelial homeostasis, defective angiogenesis and inflammation are implicated. Angiopoietin 2 (Ang2) impairs acute thrombus resolution and is associated with vasculopathy in idiopathic pulmonary arterial hypertension.
METHODS: We assessed circulating proteins associated with these processes in serum from patients with CTEPH (n = 71) before and after pulmonary endarterectomy (PEA), chronic thromboembolic pulmonary disease without pulmonary hypertension (CTEPD, n = 9) and healthy controls (n = 20) using Luminex multiplex arrays. Comparisons between groups were made using multivariable rank regression models. Ang2 and high-sensitivity C-reactive protein (hsCRP) were measured in a larger validation dataset (CTEPH = 277, CTEPD = 26). Cox proportional hazards models were used to identify markers predictive of survival.
RESULTS: In CTEPH patients, Ang2, interleukin (IL) 8, tumor necrosis factor α, and hsCRP were elevated compared to controls, while vascular endothelial growth factor (VEGF) c was lower (p < 0.05). Ang2 fell post-PEA (p < 0.05) and was associated with both pre- and post-PEA pulmonary hemodynamic variables and functional assessments (p < 0.05). In the validation dataset, Ang2 was significantly higher in CTEPH compared to CTEPD. Pre-operative hsCRP was an independent predictor of mortality.
CONCLUSIONS: We hypothesize that CTEPH patients have significant distal micro-vasculopathy and consequently high circulating Ang2. Patients with CTEPD without pulmonary hypertension have no discernible distal micro-vasculopathy and therefore have low circulating Ang2. This suggests Ang2 may be critical to CTEPH disease pathogenesis (impaired thrombus organization and disease severity).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation - 42(2023), 3 vom: 04. März, Seite 398-405 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hadinnapola, Charaka M [VerfasserIn] |
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| Links: |
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| Themen: |
9007-41-4 |
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| Anmerkungen: |
Date Completed 26.02.2023 Date Revised 02.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.healun.2022.08.021 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM351201920 |
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| 041 | |a eng | ||
| 100 | 1 | |a Hadinnapola, Charaka M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Angiopoietin 2 and hsCRP are associated with pulmonary hemodynamics and long-term mortality respectively in CTEPH-Results from a prospective discovery and validation biomarker study |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 26.02.2023 | ||
| 500 | |a Date Revised 02.03.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed disease of uncertain etiology. Altered endothelial homeostasis, defective angiogenesis and inflammation are implicated. Angiopoietin 2 (Ang2) impairs acute thrombus resolution and is associated with vasculopathy in idiopathic pulmonary arterial hypertension | ||
| 520 | |a METHODS: We assessed circulating proteins associated with these processes in serum from patients with CTEPH (n = 71) before and after pulmonary endarterectomy (PEA), chronic thromboembolic pulmonary disease without pulmonary hypertension (CTEPD, n = 9) and healthy controls (n = 20) using Luminex multiplex arrays. Comparisons between groups were made using multivariable rank regression models. Ang2 and high-sensitivity C-reactive protein (hsCRP) were measured in a larger validation dataset (CTEPH = 277, CTEPD = 26). Cox proportional hazards models were used to identify markers predictive of survival | ||
| 520 | |a RESULTS: In CTEPH patients, Ang2, interleukin (IL) 8, tumor necrosis factor α, and hsCRP were elevated compared to controls, while vascular endothelial growth factor (VEGF) c was lower (p < 0.05). Ang2 fell post-PEA (p < 0.05) and was associated with both pre- and post-PEA pulmonary hemodynamic variables and functional assessments (p < 0.05). In the validation dataset, Ang2 was significantly higher in CTEPH compared to CTEPD. Pre-operative hsCRP was an independent predictor of mortality | ||
| 520 | |a CONCLUSIONS: We hypothesize that CTEPH patients have significant distal micro-vasculopathy and consequently high circulating Ang2. Patients with CTEPD without pulmonary hypertension have no discernible distal micro-vasculopathy and therefore have low circulating Ang2. This suggests Ang2 may be critical to CTEPH disease pathogenesis (impaired thrombus organization and disease severity) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CTEPH | |
| 650 | 4 | |a angiogenesis | |
| 650 | 4 | |a angiopoietin 2 | |
| 650 | 4 | |a inflammation | |
| 650 | 7 | |a Angiopoietin-2 |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a C-Reactive Protein |2 NLM | |
| 650 | 7 | |a 9007-41-4 |2 NLM | |
| 650 | 7 | |a Vascular Endothelial Growth Factor A |2 NLM | |
| 700 | 1 | |a Southwood, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Hernández-Sánchez, Jules |e verfasserin |4 aut | |
| 700 | 1 | |a Bunclark, Katherine |e verfasserin |4 aut | |
| 700 | 1 | |a Newnham, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Swietlik, Emilia M |e verfasserin |4 aut | |
| 700 | 1 | |a Cannon, John |e verfasserin |4 aut | |
| 700 | 1 | |a Preston, Stephen D |e verfasserin |4 aut | |
| 700 | 1 | |a Sheares, Karen |e verfasserin |4 aut | |
| 700 | 1 | |a Taboada, Dolores |e verfasserin |4 aut | |
| 700 | 1 | |a Screaton, Nicholas |e verfasserin |4 aut | |
| 700 | 1 | |a Jenkins, David P |e verfasserin |4 aut | |
| 700 | 1 | |a Morrell, Nicholas W |e verfasserin |4 aut | |
| 700 | 1 | |a Toshner, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Pepke-Zaba, Joanna |e verfasserin |4 aut | |
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