Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension.
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.
Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands.
G
G
Ghobadi
B
B
Bartelds
S J
SJ
van der Veen
M G
MG
Dickinson
S
S
Brandenburg
R M F
RM
Berger
J A
JA
Langendijk
R P
RP
Coppes
P
P
van Luijk
D000704:Analysis of Variance; D000818:Animals; D004487:Edema / Q000473:pathology; D004730:Endothelium, Vascular / Q000528:radiation effects; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000473:pathology*; D016014:Linear Models; D008168:Lung / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D011522:Protons; D011651:Pulmonary Artery / Q000528:radiation effects*; D011832:Radiation Injuries / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D011522:Protons