Abstract
Provirus integration site for Moloney murine leukemia virus (Pim-1) is an oncoprotein overexpressed in lungs from pulmonary arterial hypertension (PAH) patients and involved in cell proliferation via the activation of the NFAT/STAT3 signaling pathway. We hypothesized that Pim-1 plasma levels would predict the presence of PAH and correlate with disease severity. Pim-1 plasma levels were measured at the time of catheterization in 49 PAH patients, including nonvasoreactive ( n = 19) and vasoreactive idiopathic PAH (n = 5), and PAH related to connective tissue disease (n = 16) and congenital heart disease (n = 9). Fifty controls were also recruited. The capacity of Pim-1 to discriminate PAH from controls and its association with disease severity were assessed. Pim-1 plasma levels were higher in PAH than in controls (9.6 ± 4.0 vs. 7.2 ± 2.4 ng/mL, P < 0.01). Pim-1 appropriately discriminated proliferative PAH from controls (AUC = 0.78 to 0.94 using ROC curves). Among PAH patients, Pim-1 correlated with traditional markers of PAH severity. The 1-year survival was 97% and 47% for PAH patients with baseline Pim-1 levels lower and higher than 11.1 ng/mL, respectively (HR 11.4 (3.3-39.7); P < 0.01). After adjustment for hemodynamic and biochemical variables, Pim-1 levels remained an independent predictor of mortality (P < 0.01). Pim-1 is a promising new biomarker in PAH.