IntroductionAngiopoietins are involved in blood-vessel maturation and stabilization through activation of the sélective endo-thelial-specific receptor Tie2, which leads to inhibition of endothelial cell (EC) prolifération and induces release of endothe-lial-derived growth factors. Récent studies suggest that altérations in the Ang 1/Tie2 pathway may contribute to pulmonary artery smooth muscle cell (PA-SMC) hyperplasia in idiopathic pulmonary hypertension (IPH).MethodsIn the présent study, we used lung homogenates and cultured cells (PA-EC and PA-SMC) from patients with IPH and controls to examine expression of angiopoietins (Angl and Ang 2) and Tie2 receptors, as well as the conséquences of Tie2 receptor activation on release of serotonin, endothelin-1, EGF, and PDGF-BB from PA-EC.ResultsWe found that expression of Angl and Ang2 (quantitative RT/PCR and Western blot for détermination of mRNA and protein, respectively) in lungs and PA-SMCs did not differ between IPH patients and controls. Tie2 receptor expression (mRNA and protein) was 3-4 fold higher in lungs and cultured PA-EC from patients with IPH than from controls (p < 0.001). Increasing doses of Angl (1-100 ng/ml) applied to PA-ECs induced dose-dependent increases in the release of serotonin and endothelin-1, which were of greater magnitude with PA-ECs from IPH patients than from controls.ConclusionThe results show that an increase in Angl-induced activation of Tie2 receptors in IPH is responsible for increased production of growth factors acting on PA-SMC.