PT  - JOURNAL ARTICLE
AU  - Christine Veith
AU  - Werner Seeger
AU  - Norbert Weissmann
AU  - Grazyna Kwapiszewska
TI  - Involvement of cytoskeletal protein paxillin in the pathogenesis of pulmonary hypertension
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p3344
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p3344.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p3344.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Pulmonary arterial hypertension (PAH) is a fatal disease characterised by a pronounced remodelling of the pulmonary vasculature. The remodelling process entails deposition of the extracellular matrix (ECM) proteins, proliferation of pulmonary arterial smooth muscle cells (PASMC), and changes in the composition of cytoskeletal proteins. Paxillin is one of the most important cytoskeletal proteins, mediating protein-protein interactions and consequently modulating cell signalling. In this study we have investigated the contribution of Paxillin in vascular remodelling.In lungs of IPAH patients we detected enhanced Paxillin expression compared to controls on both mRNA and protein levels. Immunohistochemical analysis demonstrated expression of Paxillin in pulmonary vasculature and PASMC. Similarly, in the hypoxia mouse model of pulmonary hypertension, expression of Paxillin was localised to the vessels. Laser microdissection of intrapulmonary arteries revealed elevated Paxillin expression in hypoxic lung vessels. Functional measurements were performed by silencing Paxillin expression. Paxillin knockdown caused changes in the phosphorylation status of Akt, and Erk1/2 leading to decreased cell viability, proliferation as well as increased apoptosis of human primary PASMC. Furthermore, immunofluorescence of PASMC revealed that Paxillin knockdown led to cytoskeletal alterations and impaired cell adhesion.Paxillin has previously been documented to be involved in cell spreading and migration, features characteristic of vascular remodelling. This is however the first report that indicates the involvement of Paxillin in vascular remodelling in the lung, and its association with human PAH disease.