The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy
Pulmonary hypertension (PH) is characterized by increased pulmonary arterial pressure caused by the accumulation of mesenchymal-like cells in the pulmonary vasculature. PH can lead to right ventricular hypertrophy (RVH) and, ultimately, heart failure and death. In PH etiology, endothelial-to-mesench...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-7737/11/1/118 |
| _version_ | 1797495676667428864 |
|---|---|
| author | Maria Laggner Philipp Hacker Felicitas Oberndorfer Jonas Bauer Thomas Raunegger Christian Gerges Tamás Szerafin Jürgen Thanner Irene Lang Nika Skoro-Sajer Hendrik Jan Ankersmit Bernhard Moser |
| author_facet | Maria Laggner Philipp Hacker Felicitas Oberndorfer Jonas Bauer Thomas Raunegger Christian Gerges Tamás Szerafin Jürgen Thanner Irene Lang Nika Skoro-Sajer Hendrik Jan Ankersmit Bernhard Moser |
| author_sort | Maria Laggner |
| collection | DOAJ |
| description | Pulmonary hypertension (PH) is characterized by increased pulmonary arterial pressure caused by the accumulation of mesenchymal-like cells in the pulmonary vasculature. PH can lead to right ventricular hypertrophy (RVH) and, ultimately, heart failure and death. In PH etiology, endothelial-to-mesenchymal transition (EndMT) has emerged as a critical process governing the conversion of endothelial cells into mesenchymal cells, and S100A4, EGF, and EGFR are implicated in EndMT. However, a potential role of S100A4, EGF, and EGFR in PH has to date not been elucidated. We therefore quantified S100A4, EGF, and EGFR in patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH). To determine specificity for unilateral heart disease, the EndMT biomarker signature was further compared between PH patients presenting with RVH and patients suffering from aortic valve stenosis (AVS) with left ventricular hypertrophy. Reduced S100A4 concentrations were found in CTEPH and iPAH patients with RVH. Systemic EGF was increased in CTEPH but not in iPAH, while AVS patients displayed slightly diminished EGF levels. EGFR was downregulated in all patient groups when compared to healthy controls. Longitudinal data analysis revealed no effect of surgical therapies on EndMT markers. Pulmonary thrombo-endarterectomized samples were devoid of S100A4, while S100A4 tissue expression positively correlated with higher grades of Heath–Edwards histopathological lesions of iPAH-derived lung tissue. Histologically, EGFR was not detectable in CTEPH lungs or in iPAH lesions. Together, our data suggest an intricate role for S100A4 and EGF/EGFR in PH with right heart pathology. |
| first_indexed | 2024-03-10T01:53:03Z |
| format | Article |
| id | doaj.art-8ba75f8c1b6d441590522a2f4e82cd1a |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T01:53:03Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-8ba75f8c1b6d441590522a2f4e82cd1a2023-11-23T13:01:30ZengMDPI AGBiology2079-77372022-01-0111111810.3390/biology11010118The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular HypertrophyMaria Laggner0Philipp Hacker1Felicitas Oberndorfer2Jonas Bauer3Thomas Raunegger4Christian Gerges5Tamás Szerafin6Jürgen Thanner7Irene Lang8Nika Skoro-Sajer9Hendrik Jan Ankersmit10Bernhard Moser11Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Oral and Maxillofacial Surgery, University Hospital St. Pölten, 3100 St. Pölten, AustriaDepartment of Pathology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, AustriaDivision of Internal Medicine and Cardiology, Klinikum Klagenfurt am Wörthersee, 9020 Klagenfurt, AustriaDepartment of Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Cardiac Surgery, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryDepartment of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, AustriaPulmonary hypertension (PH) is characterized by increased pulmonary arterial pressure caused by the accumulation of mesenchymal-like cells in the pulmonary vasculature. PH can lead to right ventricular hypertrophy (RVH) and, ultimately, heart failure and death. In PH etiology, endothelial-to-mesenchymal transition (EndMT) has emerged as a critical process governing the conversion of endothelial cells into mesenchymal cells, and S100A4, EGF, and EGFR are implicated in EndMT. However, a potential role of S100A4, EGF, and EGFR in PH has to date not been elucidated. We therefore quantified S100A4, EGF, and EGFR in patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH). To determine specificity for unilateral heart disease, the EndMT biomarker signature was further compared between PH patients presenting with RVH and patients suffering from aortic valve stenosis (AVS) with left ventricular hypertrophy. Reduced S100A4 concentrations were found in CTEPH and iPAH patients with RVH. Systemic EGF was increased in CTEPH but not in iPAH, while AVS patients displayed slightly diminished EGF levels. EGFR was downregulated in all patient groups when compared to healthy controls. Longitudinal data analysis revealed no effect of surgical therapies on EndMT markers. Pulmonary thrombo-endarterectomized samples were devoid of S100A4, while S100A4 tissue expression positively correlated with higher grades of Heath–Edwards histopathological lesions of iPAH-derived lung tissue. Histologically, EGFR was not detectable in CTEPH lungs or in iPAH lesions. Together, our data suggest an intricate role for S100A4 and EGF/EGFR in PH with right heart pathology.https://www.mdpi.com/2079-7737/11/1/118pulmonary hypertensionchronic thromboembolic pulmonary hypertensionidiopathic pulmonary arterial hypertensionS100A4epidermal growth factorepidermal growth factor receptor |
| spellingShingle | Maria Laggner Philipp Hacker Felicitas Oberndorfer Jonas Bauer Thomas Raunegger Christian Gerges Tamás Szerafin Jürgen Thanner Irene Lang Nika Skoro-Sajer Hendrik Jan Ankersmit Bernhard Moser The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy Biology pulmonary hypertension chronic thromboembolic pulmonary hypertension idiopathic pulmonary arterial hypertension S100A4 epidermal growth factor epidermal growth factor receptor |
| title | The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy |
| title_full | The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy |
| title_fullStr | The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy |
| title_full_unstemmed | The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy |
| title_short | The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy |
| title_sort | roles of s100a4 and the egf egfr signaling axis in pulmonary hypertension with right ventricular hypertrophy |
| topic | pulmonary hypertension chronic thromboembolic pulmonary hypertension idiopathic pulmonary arterial hypertension S100A4 epidermal growth factor epidermal growth factor receptor |
| url | https://www.mdpi.com/2079-7737/11/1/118 |
| work_keys_str_mv | AT marialaggner therolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT philipphacker therolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT felicitasoberndorfer therolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT jonasbauer therolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT thomasraunegger therolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT christiangerges therolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT tamasszerafin therolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT jurgenthanner therolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT irenelang therolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT nikaskorosajer therolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT hendrikjanankersmit therolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT bernhardmoser therolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT marialaggner rolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT philipphacker rolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT felicitasoberndorfer rolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT jonasbauer rolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT thomasraunegger rolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT christiangerges rolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT tamasszerafin rolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT jurgenthanner rolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT irenelang rolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT nikaskorosajer rolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT hendrikjanankersmit rolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy AT bernhardmoser rolesofs100a4andtheegfegfrsignalingaxisinpulmonaryhypertensionwithrightventricularhypertrophy |