Résumé
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.