RT Journal Article
SR Electronic
T1 Pulmonary hypertension in smoking mice over-expressing protease-activated receptor-2
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP erj00602-2010
DO 10.1183/09031936.00060210
A1 G. De Cunto
A1 S. Cardini
A1 G. Cirino
A1 P. Geppetti
A1 G. Lungarella
A1 M. Lucattelli
YR 2010
UL http://erj.ersjournals.com/content/early/2010/08/06/09031936.00060210.abstract
AB The mechanism(s) involved in the development of pulmonary hypertension (PH) in COPD is still object of investigation. Cigarette smoke (CS) may lead to remodelling of intrapulmonary vessels and dynamic changes in vascular function, at least in some smokers. A role for proteases in PH has been recently put forward.We investigated in smoking mice the role of protease-activated receptor-2 (PAR-2) in the pathogenesis of PH associated with emphysema.We demonstrate that CS exposure can modulate PAR-2 expression in mouse lung.Acute CS exposure induces in WT and in transgenic mice over-expressing PAR-2 (FVBPAR−2−TgN) a similar degree of neutrophil influx in bronchoalveolar lavage fluids.After chronic CS exposure WT and FVBPAR−2−TgN mice show emphysema, but only transgenic mice develop muscularization of small intrapulmonary vessels that precedes the development of PH (∼45% increase) and right ventricular hypertrophy. Smoking in FVBPAR−2−TgN mice results in an imbalance between vasoconstrictors (especially ET-1) and vasodilators (i.e. VEGF, eNOS and iNOS) and enhanced production of growth factors involved both in fibroblast-smooth muscle cell transaction (PDGF and TGFβ) and vascular cell proliferation (PDGF).PAR-2 signalling can influence the production and release of many factors, which may play a role in the development of PH in smokers.