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Published ahead of print on June 23, 2004, doi:10.1164/rccm.200312-1686OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 8, October 2004, 911-919

A more recent version of this article appeared on October 15, 2004
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Submitted on December 16, 2003
Accepted on June 19, 2004

Gene Microarray Analysis of Peripheral Blood Cells in Pulmonary Arterial Hypertension

Todd M Bull1*, Christopher D Coldren1, Mark Moore1, Sylk M Sotto-Santiago1, David V Pham1, S. Patrick Nana-Sinkam1, Norbert F Voelkel1, and Mark W Geraci1

1 Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Pulmonary Hypertension Center, Denver, CO, USA

* To whom correspondence should be addressed. E-mail: Todd.Bull{at}uchsc.edu.

The importance of genetic predisposition, inflammation and autoimmune mechanisms in the development of pulmonary arterial hypertension is becoming increasingly clear. We hypothesized that the analysis of gene expression profiles from peripheral blood mononuclear cells would distinguish patients with pulmonary arterial hypertension from normal volunteers. We also hypothesized that a sub-set of genes would discriminate between patients with idiopathic pulmonary arterial hypertension and pulmonary hypertension related to secondary causes. Mononuclear cells were isolated from 15 patients diagnosed with pulmonary arterial hypertension and 6 normal controls. Microarray expression was performed and the expression profiles were analyzed for consistent and predictive differences in gene expression. We identified a signature set of 106 genes which discriminated between patients with pulmonary arterial hypertension and normal individuals with high certainty (p≤0.002). The results of the microarray analysis were retrospectively and prospectively confirmed by q-PCR for 2 of the 106 genes. Supervised clustering analysis generated a list of differentially expressed genes between patients with idiopathic and secondary causes of pulmonary hypertension. Microarray expression profiling of peripheral blood cells can discriminate between patients with pulmonary arterial hypertension and normal volunteers. These findings may have important implications towards diagnosis, screening and pathogenesis of this disease.
Key words: Gene microarray, pulmonary arterial hypertension, mononuclear cells, plexiform lesion, biomarker




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