TGF- type II receptor in pulmonary arteries of patients with very severe COPD

¹ Dept of Cardiologic, Thoracic and Vascular Sciences, Section of Respiratory Diseases, University of Padova
² Institute of Pathology, University of Padova
³ Dept of Environmental Medicine and Public Health, University of Padova
⁴ Dept of Oncology and Haemathology, University of Modena and Reggio Emilia, Italy

^* To whom correspondence should be addressed. E-mail: marina.saetta{at}unipd.it.

	Abstract

A mild-moderate increase of pulmonary artery pressure is often associated with severe chronic obstructive pulmonary disease (COPD). Transforming growth factor- is a cytokine involved in the maintenance of integrity of vasculature. To investigate whether the TGF- pathway may be involved in the development of pulmonary hypertension associated with COPD, we examined surgical specimens from 14 patients undergoing lung transplantation for very severe COPD (FEV₁ 17±2% predicted) and from 7 donors. With immunohistochemistry, we quantified the expression of TGF-1 and TGF- type II receptor (TGF-RII), the cell proliferation index and structural changes in pulmonary arteries. In severe COPD patients, we observed an increased expression of TGF-RII (p<0.05) both in tunica media and intima, which was associated with a normal proliferation index in both layers. Conversely, we observed a significant thickening in tunica intima, that was not present in tunica media, suggesting that mechanisms other than cell proliferation may be involved in intimal thickening. In conclusion, in pulmonary arteries of patients with severe COPD, there is an upregulation of TGF-RII associated to a normal proliferation index. These findings suggest the activation of an antiproliferative pathway, which might explain the relative low degree of pulmonary hypertension observed in these subjects.

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