ICAM-1 promotes the abnormal endothelial cell phenotype in chronic thromboembolic pulmonary hypertension.

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2019 Sep

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Pulmonary endothelial cells play a key role in the pathogenesis of Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Increased synthesis and/or the release of intercellular adhesion molecule-1 (ICAM-1) by pulmonary endothelial cells of patients with CTEPH has been recently reported, suggesting a potential role for ICAM-1 in CTEPH. We studied pulmonary endarterectomy specimens from 172 patients with CTEPH and pulmonary artery specimens from 97 controls undergoing lobectomy for low-stage cancer without metastasis. ICAM-1 was overexpressed in vitro in isolated and cultured endothelial cells from endarterectomy specimens. Endothelial cell growth and apoptosis resistance were significantly higher in CTEPH specimens than in the controls (p < 0.001). Both abnormalities were abolished by pharmacological inhibition of ICAM-1 synthesis or activity. The overexpression of ICAM-1 contributed to the acquisition and maintenance of abnormal EC growth and apoptosis resistance via the phosphorylation of SRC, p38 and ERK1/2 and the overproduction of survivin. Regarding the ICAM-1 E469K polymorphism, the KE heterozygote genotype was significantly more frequent in CTEPH than in the controls, but it was not associated with disease severity among patients with CTEPH. ICAM-1 contributes to maintaining the abnormal endothelial cell phenotype in CTEPH. Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Citation

Jennifer Arthur Ataam, Olaf Mercier, Lilia Lamrani, Myriam Amsallem, Joanna Arthur Ataam, Stephanie Arthur Ataam, Julien Guihaire, Florence Lecerf, Véronique Capuano, Maria Rosa Ghigna, François Haddad, Elie Fadel, Saadia Eddahibi. ICAM-1 promotes the abnormal endothelial cell phenotype in chronic thromboembolic pulmonary hypertension. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2019 Sep;38(9):982-996