ICAM-1 PROMOTES THE ABNORMAL ENDOTHELIAL CELLPHENOTYPE IN CHRONIC THROMBOEMBOLIC PULMONARYHYPERTENSION

Jennifer Arthur Ataam , Olaf Mercier (1, 2) , Lilia Lamrani (1) , Myriam Amsallem (1) , Joanna Arthur-Ataam (3) , Stéphanie Arthur-Ataam (1) , Julien Guihaire (1, 2) , Florence Lecerf (1, 2) , Véronique Capuano (1, 2) , Maria Rosa Ghigna (1, 2) , François Haddad , Elie Fadel (2) , Saadia Eddahibi (3)

1 Hôpital Marie-Lannelongue
2 HPPIT - Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique
3 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]

BACKGROUND - Pulmonary endothelial cells play a key role in the pathogenesis of ChronicThromboembolic Pulmonary Hypertension (CTEPH). Increased synthesis and/or release ofIntercellular Adhesion Molecule 1 (ICAM-1) by pulmonary endothelial cells of patients withCTEPH has been recently reported, suggesting a potential role for ICAM-1 in CTEPH.METHODS - We studied pulmonary endarterectomy specimens from 172 patients with CTEPHand pulmonary artery specimens from 97 controls undergoing lobectomy for low-stage cancerwithout metastasis.RESULTS - ICAM-1 was overexpressed in vitro in isolated and cultured endothelial cells fromendarterectomy specimens. Endothelial cell (EC) growth and apoptosis resistance weresignificantly higher in CTEPH specimens than in controls (P<0.001). Both abnormalities wereabolished by pharmacological inhibition of ICAM-1 synthesis or activity. Overexpression ofICAM-1 contributed to the acquisition and maintenance of abnormal EC growth and apoptosisresistance via phosphorylation of SRC, p38 and ERK1/2 and overproduction of Survivin.Regarding the ICAM-1 E469K polymorphism, the KE heterozygote genotype was significantlymore frequent in CTEPH than in controls, but was not associated with disease severity amongpatients with CTEPH.CONCLUSIONS - ICAM-1 contributes to maintaining the abnormal endothelial cell phenotypein CTEPH.

Domaines: Sciences du Vivant [q-bio]

Jennifer Arthur Ataam, Olaf Mercier, Lilia Lamrani, Myriam Amsallem, Joanna Arthur-Ataam, et al.. ICAM-1 PROMOTES THE ABNORMAL ENDOTHELIAL CELLPHENOTYPE IN CHRONIC THROMBOEMBOLIC PULMONARYHYPERTENSION. The Journal of Heart and Lung Transplantation, In press, ⟨10.1016/j.healun.2019.06.010⟩. ⟨hal-02165685⟩