Angiostatic Factors in the Pulmonary Endarterectomy Material from Chronic Thromboembolic Pulmonary Hypertension Patients Cause Endothelial Dysfunction
Open Access
- 20 August 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (8), e43793
- https://doi.org/10.1371/journal.pone.0043793
Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease with persistent thrombotic occlusion or stenosis of the large pulmonary arteries resulting in pulmonary hypertension. Surgical removal of the neointimal layer of these vessels together with the non-resolved thrombus consisting of organized collagen-rich fibrotic areas with partly recanalized regions is the treatment of choice (pulmonary endarterectomy, PEA). The present study investigates endothelial cells isolated from such material as well as factors present in the surgical PEA material, which may contribute to impairment of recanalization and thrombus non-resolution. We observed muscularized vessels 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 (ELISA) as well as on the tissue level (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 PF4 and IP-10, 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 the cell proliferation, migration and vessel formation in hPAECs. The presence of angiostatic factors like PF4, collagen type I and IP-10, as recovered from the surgical PEA material from CTEPH patients, may lead to changes in calcium homeostasis and endothelial dysfunction.Keywords
This publication has 63 references indexed in Scilit:
- Endothelial-like cells in chronic thromboembolic pulmonary hypertension: crosstalk with myofibroblast-like cellsRespiratory Research, 2011
- Platelet factor-4 and its p17-70 peptide inhibit myeloma proliferation and angiogenesis in vivoBMC Cancer, 2011
- Angiostatic and chemotactic activities of the CXC chemokine CXCL4L1 (platelet factor-4 variant) are mediated by CXCR3Blood, 2011
- Multipotent mesenchymal progenitor cells are present in endarterectomized tissues from patients with chronic thromboembolic pulmonary hypertensionAmerican Journal of Physiology-Cell Physiology, 2010
- Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2CNature Genetics, 2009
- Inhibition of mTOR attenuates store-operated Ca2+ entry in cells from endarterectomized tissues of patients with chronic thromboembolic pulmonary hypertensionAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2009
- IP-10 induces dissociation of newly formed blood vesselsJournal of Cell Science, 2009
- Identification of putative endothelial progenitor cells (CD34+CD133+Flk-1+) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertensionAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2009
- Chronic exposure to fibrin and fibrinogen differentially regulates intracellular Ca2+ in human pulmonary arterial smooth muscle and endothelial cellsAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2009
- Techniques and Outcomes of Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary HypertensionProceedings of the American Thoracic Society, 2006