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Published online before print May 31, 2006, 10.1183/09031936.06.00077105
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Eur Respir J 2006; 28:556-562
Copyright ©ERS Journals Ltd 2006

Transforming growth factor-ß type II receptor in pulmonary arteries of patients with very severe COPD

B. Beghe1, E. Bazzan1, S. Baraldo1, F. Calabrese2, F. Rea1, M. Loy1, P. Maestrelli3, R. Zuin1, L. M. Fabbri4 and M. Saetta1

1 Dept of Cardiological, Thoracic and Vascular Sciences, Section of Respiratory Diseases, 2 Institute of Pathology, and 3 Dept of Environmental Medicine and Public Health,, University of Padua, Padua, and 4 Dept of Oncology and Haematology, University of Modena and Reggio Emilia, Modena and Reggio Emilia, Italy.

CORRESPONDENCE: M. Saetta, Divisione di Pneumologia, Dipartimento di Scienze Cardiologiche, Toraciche e Vascolari, via Giustiniani 3, 35128 Padova, Italy. Fax: 39 0498213701. E-mail: marina.saetta{at}unipd.it

Keywords: Cytokines, emphysema, lung transplantation, pulmonary hypertension, vascular remodelling

Received: July 1, 2005
Accepted May 4, 2006

A mild-to-moderate increase in pulmonary arterial pressure is often associated with severe chronic obstructive pulmonary disease (COPD). Transforming growth factor (TGF)-ß is a cytokine involved in the maintenance of integrity of vasculature. The aim of the study was to investigate whether the TGF-ß pathway might be involved in the development of pulmonary hypertension associated with COPD.

Surgical specimens from 14 patients undergoing lung transplantation for very severe COPD (forced expiratory volume in one second 17±2% of the predicted value) and from seven donors were examined. The expression of TGF-ß1 and TGF-ß type II receptor (TGF-ßRII), cell proliferation index and structural changes in pulmonary arteries were quantified immunohistochemically.

In severe COPD patients, increased expression of TGF-ßRII was observed in both the tunica media and intima, which was associated with a normal proliferation index in both layers. Conversely, significant thickening of the tunica intima, which was not present in the tunica media, was observed, suggesting that mechanisms other than cell proliferation may be involved in intimal thickening.

In conclusion, in the pulmonary arteries of patients with severe chronic obstructive pulmonary disease, there is upregulation of transforming growth factor-ß type II receptor expression associated with a normal proliferation index. These findings suggest the activation of an antiproliferative pathway, which might explain the relatively low degree of pulmonary hypertension observed in these subjects.




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