Impact of angiopoietin-1 and -2 on clinical course of idiopathic pulmonary fibrosis

Respir Med. 2016 May:114:18-26. doi: 10.1016/j.rmed.2016.03.001. Epub 2016 Mar 5.


Background: Angiopoietin (Ang) -1 and -2 are glycoproteins that play roles in vascular development, angiogenesis, and lung vascular permeability. Although the serum concentrations of Ang-1 and -2 have been evaluated in patients with sepsis, those in patients with idiopathic pulmonary fibrosis (IPF) have received less attention.

Objective: To elucidate the clinical significance of Ang-1 and -2 in patients with IPF.

Methods: Seventy-five patients with IPF were retrospectively studied. Serum concentrations of Ang-1 and -2 at diagnosis of IPF were measured by enzyme-linked immunosorbent assay. The relationships of the Ang-1 and -2 concentrations with pulmonary function test results, high-resolution computed tomography findings, histologic findings, occurrence of acute exacerbation of IPF (AE-IPF), and prognosis were evaluated.

Results: The median patient age was 68 year-old and the median observation period was 44 months. IPF patients with high Ang-2 concentrations showed a significantly lower forced vital capacity (FVC) (2.28 vs. 2.69 L, respectively; p = 0.047) and lower percent diffusion lung capacity for carbon monoxide (%DLCO) (61.4 vs. 81.4%, respectively; p = 0.015) than patients with low Ang-2 concentrations. Serum Ang-2 concentrations were negatively correlated with %DLCO (r = -0.375, p = 0.021) and the change in %FVC in 12 months (r = -0.348, p = 0.043). The Ang-2 concentration was significantly higher in several patients with AE-IPF than in patients in stable condition (p = 0.011). Finally, patients with high Ang-2 concentrations showed a significantly worse prognosis than those with low Ang-2 concentrations (log-rank p = 0.039). Multivariate analysis showed that the serum Ang-2 concentration, but not the Ang-1 concentration, was a significant prognostic factor in patients with IPF (hazard ratio 1.439, p = 0.028).

Conclusion: Increases in the serum Ang-2 concentration were associated with disease progression and poor prognosis in patients with IPF.

Keywords: Angiogenesis; Angiopoietin; Idiopathic pulmonary fibrosis; Usual interstitial pneumonia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inducing Agents
  • Angiopoietin-1 / blood*
  • Angiopoietin-2 / blood*
  • Carbon Monoxide / metabolism
  • Disease Progression
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / blood*
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Lung / blood supply
  • Lung / metabolism*
  • Lung / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Pulmonary Diffusing Capacity / physiology
  • Respiratory Function Tests / methods
  • Retrospective Studies
  • Tomography, X-Ray Computed
  • Vital Capacity / physiology


  • ANGPT1 protein, human
  • ANGPT2 protein, human
  • Angiogenesis Inducing Agents
  • Angiopoietin-1
  • Angiopoietin-2
  • Carbon Monoxide