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Original article
Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension
  1. G Ghobadi1,2,
  2. B Bartelds3,
  3. S J van der Veen1,2,
  4. M G Dickinson3,
  5. S Brandenburg4,
  6. R M F Berger3,
  7. J A Langendijk1,
  8. R P Coppes1,2,
  9. P van Luijk1
  1. 1Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  2. 2Department of Cell Biology, Section of Radiation and Stress Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  3. 3Center for Congenital Heart Disease, Pediatric Cardiology, Beatrix Children Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  4. 4Kernfysisch Versneller Instituut, University of Groningen, Groningen, The Netherlands
  1. Correspondence to Dr Peter van Luijk, Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands; p.van.luijk{at}umcg.nl

Abstract

Background Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an important role in the development of radiation-induced pulmonary toxicity. Therefore, the authors investigated whether irradiation of the lung also induces pulmonary hypertension.

Methods Different sub-volumes of the rat lung were irradiated with protons known to induce different levels of pulmonary vascular damage.

Results Early loss of endothelial cells and vascular oedema were observed in the irradiation field and in shielded parts of the lung, even before the onset of clinical symptoms. 8 weeks after irradiation, irradiated volume-dependent vascular remodelling was observed, correlating perfectly with pulmonary artery pressure, right ventricle hypertrophy and pulmonary dysfunction.

Conclusions The findings indicate that partial lung irradiation induces pulmonary vascular remodelling resulting from acute pulmonary endothelial cell loss and consequential pulmonary hypertension. Moreover, the close resemblance of the observed vascular remodelling with vascular lesions in PAH makes partial lung irradiation a promising new model for studying PAH.

  • Lung cancer
  • drug-induced lung disease
  • vascular remodelling
  • pulmonary hypertension
  • endothelial cell loss
  • radiation pneumonitis
  • histology/cytology
  • lung physiology
  • primary pulmonary hypertension
  • cytokine biology
  • histology/cytology
  • primary pulmonary hypertension

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Footnotes

  • Funding This work was funded by the Dutch Cancer Society (grant no. 2007-3890) and the Innovational Research Incentives Scheme of the Netherlands Organisation for Scientific Research (NWO) (grant no. 916.76.029).

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.