Circulating angiopoietins in idiopathic pulmonary arterial hypertension

Eur Heart J. 2010 Sep;31(18):2291-300. doi: 10.1093/eurheartj/ehq226. Epub 2010 Jul 2.


Aims: To determine the diagnostic utility of circulating angiopoietin-1 (Ang-1) and its antagonist angiopoietin-2 (Ang-2) as potential biomarkers of disease severity or response to treatment in idiopathic pulmonary arterial hypertension (IPAH). Imbalances in angiogenic factors including vascular endothelial cell growth factor (VEGF) and the angiopoetin-Tie2 receptor system have been implicated in the pathogenesis of IPAH.

Methods and results: Plasma Ang-1, Ang-2, soluble Tie2 (sTie2), and VEGF were determined by in-house immunoassays in two cohorts of IPAH patients: a retrospective cohort (n = 81) and a prospective cohort (n = 25). Ten patients with normal pulmonary artery pressures and 14 apparently healthy subjects served as controls. Plasma levels of all angiogenic factors were elevated in IPAH patients compared with controls (all P < 0.005). Angiopoietin-2, but not Ang-1, sTie2, and VEGF correlated with cardiac index (r = -0.53, P < 0.001), pulmonary vascular resistance (PVR) (r= 0.60, P < 0.001), and mixed venous oxygen saturation (SvO(2)) (r= -0.63, P < 0.001). In multivariate analysis, elevated Ang-2 was an independent risk factor of mortality (P = 0.004). The patients in the prospective cohort were studied longitudinally at baseline and 3 months after initiation of therapy. Changes in Ang-2 after initiation of therapy correlated with changes in mean right atrial pressure (r = 0.6, P = 0.008), PVR (r = 0.51, P = 0.04), and inversely related to changes in SvO(2) (r = -0.75, P < 0.001). Histological studies showed that the expression of Ang-2 mRNA and protein was up-regulated in plexiform lesions from IPAH lung tissue samples.

Conclusion: Ang-2 may be involved in the pathogenesis of IPAH, and plasma Ang-2 might serve as a promising new biomarker of disease severity and response to treatment in patients with IPAH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiopoietin-1 / blood*
  • Angiopoietin-2 / blood*
  • Biomarkers / blood
  • Case-Control Studies
  • Familial Primary Pulmonary Hypertension
  • Female
  • Humans
  • Hypertension, Pulmonary / blood
  • Hypertension, Pulmonary / diagnosis
  • Hypertension, Pulmonary / therapy
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Prospective Studies
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A / blood


  • Angiopoietin-1
  • Angiopoietin-2
  • Biomarkers
  • Peptide Fragments
  • Vascular Endothelial Growth Factor A
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain