Pulmonary arterial hypertension (PAH) is characterised by a fixed elevation in pulmonary artery pressure in response to intraluminal vascular cell proliferations. Bone morphogenetic protein (BMP) signalling exerts powerful mitogenic responses in vascular cells although the complete mechanisms by which dysfunctional BMP and Smad signalling contribute to vascular remodelling observed in PAH remain unloiown. Mutations in the BMPR2 gene, encoding the type II BMP receptor (BMPR-II), underlie many cases of familial PAH. Here, the BMP and Smad signalling pathway are characterised and reduced vascular BMP and Smad expression identified in human PAH lung, presumably leading to a loss of growth control over puhnonary vascular cells. To evaluate the impact of SiBMPR2 mutation during vasculogenesis or in adult PAH, gene silencmg for BMPR2 and adenoviral transfection of mutant receptor construct were used to disrupt Smad signalling and were found to interrupt endothelial cell proliferation and migration in vitro.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:490453 |
| Date | January 2008 |
| Creators | Southwood, Mark Richard |
| Publisher | University of the West of England, Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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