The presence of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is still object of research. Recent studies indicate that cigarette smoke (CS) may have, at least in some individuals, a direct effect on the intrapulmonary vessels with upregulation of mediators that lead to vascular structural remodelling and dynamic changes in vascular function. A role for proteases in PH has been recently put forward. In the present study, we examined the role of PAR-2 in the pathogenesis of lung vascular remodelling induced in mice by chronic exposure to CS. After 7 months of CS exposure, FVB mice overexpressing PAR-2 (FVBPAR-2-TgN) developed emphysema associated with PH. A marked vascular remodelling of the small intrapulmonary vessels preceded the onset of PH. Normally poorly muscularized blood vessels changed phenotype to a more muscularized type and the number of smooth muscle cells (SMC) around the small and mid-sized vessels progressively increased from 4 months onwards. No vascular changes were seen in WT mice after chronic exposure to CS. The effect of tobacco smoke in FVBPAR-2-TgN mice resulted in an imbalance between vasoconstrictors (especially ET-1) and vasodilators (i.e. VEGF, NO) and enhanced production of growth factors involved in fibroblast-SMC transaction (PDGF and TGF ) and vascular cell proliferation (PDGF ). PAR-2 signalling can influence the production and the release of many of these factors, which ultimately lead to vascular remodelling and aberrant vascular physiology. The level of expression of PAR-2 may play an important role in the development of PH in human smokers.
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|Titolo:||Pulmonary hypertension in smoking mice over-expressing protease-activated receptor-2.|
|Rivista:||EUROPEAN RESPIRATORY JOURNAL|
|Citazione:||DE CUNTO, G., Cardini, S., Cirino, G., Geppetti, P., Lungarella, G., & Lucattelli, M. (2011). Pulmonary hypertension in smoking mice over-expressing protease-activated receptor-2. EUROPEAN RESPIRATORY JOURNAL, 37(823), 834.|
|Appare nelle tipologie:||1.1 Articolo in rivista|