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Effect of BMP-2 on Pulmonary Artery Smooth Muscle Cells from Patients with Idiopathic Pulmonary Arterial Hypertension

ABSTRACT: Bone morphogenetic proteins (BMP) inhibit proliferation and induce apoptosis in pulmonary artery smooth muscle cells (PASMC) from normal subjects. Dysfunction of BMP signaling due to mutations in and/or downregulation of BMP receptors has been implicated in idiopathic pulmonary arterial hypertension (IPAH). We examined whether BMP differentially regulates gene expression in PASMC from normal subjects and IPAH patients using the Affymetrix microarray analysis. BMP-2 treatment (200 nM for 24 hrs) altered expression levels of 6,206 genes in normal and IPAH PASMC. 1,063 of these genes were regulated oppositely by BMP-2: 523 genes were downregulated by BMP-2 in normal PASMC but upregulated in IPAH PASMC, whereas 540 genes were upregulated by BMP-2 in normal PASMC but downregulated in IPAH PASMC. The divergent effects of BMP-2 on gene expression profiles indicate that PASMC may undergo significant phenotypic changes in IPAH patients during development of the disease. The transition of the antiproliferative effect of BMP-2 in normal PASMC to its proliferative effect in IPAH patients is attributed potentially to its differential effect on expression patterns of various genes that are involved in cell proliferation and apoptosis. Among the 6206 BMP-2-sensitive genes, there are more than 1800 genes whose expression levels were negatively (with a correlation coefficient, r, < –0.9) or positively (with r > +0.9) correlated with the pulmonary arterial pressure. These results suggest that BMP-mediated gene regulation is significantly altered in PASMC from IPAH patients and mRNA expression changes in BMP-regulated genes may be involved in the development of IPAH. Keywords = bone morphogenetic receptor protein Keywords = idiopathic pulmonary arterial hypertension Keywords = transcription factor Keywords = gene expression profile Keywords: other

ORGANISM(S): Homo sapiens

PROVIDER: GSE2559 | GEO | 2005/10/21

SECONDARY ACCESSION(S): PRJNA92173

REPOSITORIES: GEO

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Effect of BMP-2 on Pulmonary Artery Smooth Muscle Cells from Patients with Idiopathic Pulmonary Arterial Hypertension

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