Jennifer Arthur Ataam1, Olaf Mercier2, Lilia Lamrani3, Myriam Amsallem4, Joanna Arthur Ataam5, Stephanie Arthur Ataam3, Julien Guihaire2, Florence Lecerf3, Véronique Capuano3, Maria Rosa Ghigna6, François Haddad7, Elie Fadel2, Saadia Eddahibi5. 1. Research and Innovation Unit; Department of Medicine, Stanford University, Stanford, California. Electronic address: jennifer.arthur.ataam@gmail.com. 2. Research and Innovation Unit; Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation. 3. Research and Innovation Unit. 4. Research and Innovation Unit; Department of Medicine, Stanford University, Stanford, California. 5. Université de Montpellier, Montpellier, France. 6. Research and Innovation Unit; Department of Pathology, Marie Lannelongue Hospital, Le Plessis Robinson, France. 7. Department of Medicine, Stanford University, Stanford, California.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: ICAM-1 contributes to maintaining the abnormal endothelial cell phenotype in CTEPH.
BACKGROUND: 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. METHODS: 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. RESULTS: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-1E469K 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. CONCLUSIONS:ICAM-1 contributes to maintaining the abnormal endothelial cell phenotype in CTEPH.
Authors: Kondababu Kurakula; Valérie F E D Smolders; Olga Tura-Ceide; J Wouter Jukema; Paul H A Quax; Marie-José Goumans Journal: Biomedicines Date: 2021-01-09
Authors: Valérie F E D Smolders; Kirsten Lodder; Cristina Rodríguez; Olga Tura-Ceide; Joan Albert Barberà; J Wouter Jukema; Paul H A Quax; Marie José Goumans; Kondababu Kurakula Journal: Cells Date: 2021-03-26 Impact factor: 6.600