Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Zabini, D.
Influence of the microenvironment and the role of cytokines in chronic thromboembolic pulmonary hypertension (CTEPH)
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medical University of Graz; 2013. pp.82.
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- Autor*innen der Med Uni Graz:
- Zabini-Polzer Diana
- Betreuer*innen:
- Heinemann Akos
- Olschewski Andrea
- Altmetrics:
- Abstract:
- Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease with persistent thrombotic occlusion or stenosis of the large pulmonary arteries resulting in increased pulmonary pressure. Surgical removal of the neointimal layer of these vessels together with non-resolved thrombus consisting of organized collagen-rich fibrotic areas with partly recanalized regions is the treatment of choice (pulmonary endarterectomy, PEA). The aim of the study was to investigate the influence of the microenvironment and present inflammatory factors on the development and stabilization of the thromboembolic PEA material, leading to chronic pulmonary hypertension. We observed muscularized and non-muscularized vessels in the PEA material. The isolated endothelial cells from the PEA material showed significantly different calcium homeostasis as compared to pulmonary artery endothelial cells (hPAECs) from normal controls. In the supernatant (FACS, ELISA) as well as in the tissue (histochemical staining) of the PEA material, platelet factor 4 (PF4), collagen type I and interferon-gamma-inducible 10 kD protein (IP-10) were detected. CXCR3, the receptor for IP-10 and PF4, was particularly elevated in the distal parts of the PEA material as compared to human control lung (RT-PCR). PF4, collagen type I and IP-10 caused significant changes in calcium homeostasis and affected proliferation, migration and vessel formation of hPAECs. The presence of angiostatic factors like PF4, collagen type I and IP-10 in the surgical PEA material from CTEPH patients may lead to changes in calcium homeostasis and endothelial dysfunction. Although also angiogenic factors such as IL-8 are present in the PEA material, the angiostatic factors might be more prominent. Based on our observations we suggest that the balance between angiogenic factors and angiostatic factors is disturbed in CTEPH patients, leading to the stabilization of the thrombi.