Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

G. Ghobadi, B. Bartelds, S. J. van der Veen, M. G. Dickinson, S. Brandenburg, R. M. F. Berger, J. A. Langendijk, R. P. Coppes, P. van Luijk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)334-341
Number of pages8
JournalThorax
Volume67
Issue number4
DOIs
Publication statusPublished - Apr-2012

Keywords

  • CONGENITAL HEART-DISEASE
  • THORACIC IRRADIATION
  • RAT LUNG
  • RADIATION PNEUMONITIS
  • ENDOTHELIAL-CELLS
  • COMPUTED-TOMOGRAPHY
  • NEOINTIMAL LESIONS
  • PROGENITOR CELLS
  • CHRONIC HYPOXIA
  • BLOOD-FLOW

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