Proteomics- and Metabolomics-Based Analysis of Metabolic Changes in a Swine Model of Pulmonary Hypertension

Payel Sen; Bachuki Shashikadze; Florian Flenkenthaler; Esther Van de Kamp; Siyu Tian; Chen Meng; Michael Gigl; Thomas Fröhlich; Daphne Merkus

doi:10.3390/ijms24054870

Proteomics- and Metabolomics-Based Analysis of Metabolic Changes in a Swine Model of Pulmonary Hypertension

Payel Sen, Bachuki Shashikadze, Florian Flenkenthaler, Esther Van de Kamp, Siyu Tian, Chen Meng, Michael Gigl, Thomas Fröhlich, Daphne Merkus^*

^*Corresponding author for this work

Cardiology

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Abstract

Pulmonary vein stenosis (PVS) causes a rare type of pulmonary hypertension (PH) by impacting the flow and pressure within the pulmonary vasculature, resulting in endothelial dysfunction and metabolic changes. A prudent line of treatment in this type of PH would be targeted therapy to relieve the pressure and reverse the flow-related changes. We used a swine model in order to mimic PH after PVS using pulmonary vein banding (PVB) of the lower lobes for 12 weeks to mimic the hemodynamic profile associated with PH and investigated the molecular alterations that provide an impetus for the development of PH. Our current study aimed to employ unbiased proteomic and metabolomic analyses on both the upper and lower lobes of the swine lung to identify regions with metabolic alterations. We detected changes in the upper lobes for the PVB animals mainly pertaining to fatty acid metabolism, reactive oxygen species (ROS) signaling and extracellular matrix (ECM) remodeling and small, albeit, significant changes in the lower lobes for purine metabolism.

Original language	English
Article number	4870
Journal	International Journal of Molecular Sciences
Volume	24
Issue number	5
DOIs	https://doi.org/10.3390/ijms24054870
Publication status	Published - 2 Mar 2023

Bibliographical note

Funding Information:
This study was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 812660 (DohART-NET) (for B.S. and T.F.), the Friedrich Bauer Foundation Reg Nr-28/21 (for P.S.) as well as by the German Center for Cardiovascular Research (DZHK81Z0600207 to D.M. and P.S.) and the Dutch CardioVascular Alliance: An initiative with support of the Dutch Heart Foundation (Grants 2020B008 RECONNEXT to D.M.).

Publisher Copyright:
© 2023 by the authors.

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Proteomics- and Metabolomics-Based Analysis of Metabolic Changes in a Swine Model of Pulmonary HypertensionFinal published version, 4.97 MBLicence: CC BY

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title = "Proteomics- and Metabolomics-Based Analysis of Metabolic Changes in a Swine Model of Pulmonary Hypertension",

abstract = "Pulmonary vein stenosis (PVS) causes a rare type of pulmonary hypertension (PH) by impacting the flow and pressure within the pulmonary vasculature, resulting in endothelial dysfunction and metabolic changes. A prudent line of treatment in this type of PH would be targeted therapy to relieve the pressure and reverse the flow-related changes. We used a swine model in order to mimic PH after PVS using pulmonary vein banding (PVB) of the lower lobes for 12 weeks to mimic the hemodynamic profile associated with PH and investigated the molecular alterations that provide an impetus for the development of PH. Our current study aimed to employ unbiased proteomic and metabolomic analyses on both the upper and lower lobes of the swine lung to identify regions with metabolic alterations. We detected changes in the upper lobes for the PVB animals mainly pertaining to fatty acid metabolism, reactive oxygen species (ROS) signaling and extracellular matrix (ECM) remodeling and small, albeit, significant changes in the lower lobes for purine metabolism.",

author = "Payel Sen and Bachuki Shashikadze and Florian Flenkenthaler and {Van de Kamp}, Esther and Siyu Tian and Chen Meng and Michael Gigl and Thomas Fr{\"o}hlich and Daphne Merkus",

note = "Funding Information: This study was supported by the European Union{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska-Curie Grant Agreement No. 812660 (DohART-NET) (for B.S. and T.F.), the Friedrich Bauer Foundation Reg Nr-28/21 (for P.S.) as well as by the German Center for Cardiovascular Research (DZHK81Z0600207 to D.M. and P.S.) and the Dutch CardioVascular Alliance: An initiative with support of the Dutch Heart Foundation (Grants 2020B008 RECONNEXT to D.M.). Publisher Copyright: {\textcopyright} 2023 by the authors.",

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AU - Shashikadze, Bachuki

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AU - Van de Kamp, Esther

AU - Tian, Siyu

AU - Meng, Chen

AU - Gigl, Michael

AU - Fröhlich, Thomas

AU - Merkus, Daphne

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PY - 2023/3/2

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N2 - Pulmonary vein stenosis (PVS) causes a rare type of pulmonary hypertension (PH) by impacting the flow and pressure within the pulmonary vasculature, resulting in endothelial dysfunction and metabolic changes. A prudent line of treatment in this type of PH would be targeted therapy to relieve the pressure and reverse the flow-related changes. We used a swine model in order to mimic PH after PVS using pulmonary vein banding (PVB) of the lower lobes for 12 weeks to mimic the hemodynamic profile associated with PH and investigated the molecular alterations that provide an impetus for the development of PH. Our current study aimed to employ unbiased proteomic and metabolomic analyses on both the upper and lower lobes of the swine lung to identify regions with metabolic alterations. We detected changes in the upper lobes for the PVB animals mainly pertaining to fatty acid metabolism, reactive oxygen species (ROS) signaling and extracellular matrix (ECM) remodeling and small, albeit, significant changes in the lower lobes for purine metabolism.

AB - Pulmonary vein stenosis (PVS) causes a rare type of pulmonary hypertension (PH) by impacting the flow and pressure within the pulmonary vasculature, resulting in endothelial dysfunction and metabolic changes. A prudent line of treatment in this type of PH would be targeted therapy to relieve the pressure and reverse the flow-related changes. We used a swine model in order to mimic PH after PVS using pulmonary vein banding (PVB) of the lower lobes for 12 weeks to mimic the hemodynamic profile associated with PH and investigated the molecular alterations that provide an impetus for the development of PH. Our current study aimed to employ unbiased proteomic and metabolomic analyses on both the upper and lower lobes of the swine lung to identify regions with metabolic alterations. We detected changes in the upper lobes for the PVB animals mainly pertaining to fatty acid metabolism, reactive oxygen species (ROS) signaling and extracellular matrix (ECM) remodeling and small, albeit, significant changes in the lower lobes for purine metabolism.

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Proteomics- and Metabolomics-Based Analysis of Metabolic Changes in a Swine Model of Pulmonary Hypertension

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