P254	Microarray identification of the BMP target genes in vascular cells.
M.Ciumas, K.Montagne, M.Eyries, B.Thomas, F.Soubrier
INSERM U525, Faculté de médecine Pitié-Salpêtrière, Paris, FR.

Pulmonary hypertension (PH) is characterized by narrowing and obliteration of small pulmonary arteries leading to sustained elevation of pulmonary arterial pressure, and increase in pulmonary vascular resistance that impede the ejection of blood by the right ventricle leading to right ventricular failure. Primary PH (PPH), is the clinical term used to describe a rare and fatal condition for which no underlying cause can be found. PPH can arise as a familial (autosomal dominant, low penetrance) or as a sporadic disease with a prevalence of 1-2 per 1 000 000 individuals and affects females twice as often as males. Heterozygous germline mutations in the BMPR2 gene, encoding the bone morphogenetic protein type II receptor (BMPR-II) a member of the transforming growth factor β (TGF-β) superfamily of receptors, have been found to underlie PPH. However, the mechanisms linking the BMPR2 mutation to pulmonary hypertension are not yet identified. A comparison of four cell types: Human Umbilical Vein Endothelial Cells (HUVEC) and Human Microvascular Endothelial Cells (HMEC), Pulmonary arterial endothelial cells (PAEC) and pulmonary arterial smooth muscle cells (PASMC) was performed for the receptors of the TGF-b superfamily and for target genes of the BMP (BMP2 and BMP4) determined by microarray. By PCR and quantitative PCR it was established that BMPR-IA is absent in the PAEC, BMPR-IB is absent in the HMEC and the ActR-IIA (Activin Receptor IIA) was found to be missing in PAEC and PASMC, while all the other receptors were detected in these cells. The induction of gene expression (Id1, Id2 Id3, EPAS1) and the repression of the gene expression (ID4, CEBPδ) were observed in the HMEC treated with BMP2 and BMP4. Microarray experiments on the PAEC and PASMC treated with two ligands are in progress and the results are being evaluated. Identification of BMP target genes in vascular cells could help elucidating the molecular mechanism of PAH and consider new therapeutically targets.

Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher.