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TRP X15 Role of endothelial cells in CTEPH

Funding period: 01.01.2018 - 31.08.2020

Project Summary

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) represents an inadequate healing response to pulmonary embolism resulting in excessive thrombofibrotic remodeling and major artery obstruction. It is still unknown why pulmonary thromboemboli are resistant to resolution and also, what maybe the exact molecular stimulus underlying the excessive pulmonary artery remodeling. Clinical and experimental evidence suggests that misguided chronic fibrotic response to unresolved pulmonary embolism or in situ fibrosis is a cause of CTEPH. Defects of the pro-fibrotic transforming growth factorbeta (TGFβ) pathway have been implicated in pulmonary arterial hypertension, whereas its role in CTEPH is unknown. One of the mechanisms induced by TGFβ signaling is endothelial-to-mesenchymal transition (EndMT), a process where endothelial cells transform into myofibroblasts. Our preliminary results show upregulated expression levels of TGFβ signaling molecules, such as endoglin, TGFβRII, BMPRII and TGFβ1 in endothelial cells in the CTEPH tissue or isolated from it. Additionally, we recently found that mediators involved in TGFβsignaling, such as SerpinG1, Periostin (POSTN), transforming growth factor-beta induced (TGFβI) and follistatin-related protein 3 (FSTL3) are upregulated in CTEPH endothelial cells (CTEPH-ECs) outgrown from the CTEPH specimens. In general, it has been shown that TGFβ family proteins play crucial role in cell physiology, the developing embryo and the adult organism. In the present project, I therefore propose to examine the role of TGFβ and TGFβ-mediated signaling, and in particular the above-mentioned TGFβ-related molecules in the process of vascular remodeling, during healthy angiogenesis using retina model but also for chronic tissue remodeling. Findings in human specimens will be further analyzed in genetically modified mice after induction of venous thrombosis by inferior Vena cava ligation. 

Principle Investigator

 Magdalena Bochenek, PhD
Magdalena Bochenek, PhD

Post Doc, Laboratory for „Translational Vascular Biology“

06131 17-8026

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