Gene Microarray Analysis of Peripheral Blood Cells in Pulmonary Arterial Hypertension

Abstract

The importance of genetic predisposition, inflammation, and autoimmune mechanisms in the development of pulmonary arterial hypertension (PAH) is becoming increasingly clear. We hypothesized that the analysis of gene expression profiles from peripheral blood mononuclear cells would distinguish patients with PAH from normal volunteers. We also hypothesized that a subset of genes would discriminate between patients with idiopathic PAH and pulmonary hypertension related to secondary causes. Mononuclear cells were isolated from 15 patients diagnosed with PAH and 6 normal control subjects. 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 that discriminated with high certainty (p < or = 0.002) between patients with PAH and normal individuals. The results of the microarray analysis were retrospectively and prospectively confirmed by quantitative polymerase chain reaction 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 PAH and normal volunteers. These findings may have important implications toward diagnosis, screening, and pathogenesis of this disease.

Pathology of Pulmonary Hypertension

“…We forecast that the pathogenetic insights will allow one to further reclassify the disease as angioproliferative [120] or myofibroblastic (as in idiopathic pulmonary fibrosis), neoplastic-like, or a reaction to injury, with clear implications to biomarker discovery, disease-tailored therapies, genetic association studies, etc. Based solely on the advances in the past 10 years, there is the potential to refine the diagnostic tools using genomics of peripheral blood cells of PH patients [121] and also to breakdown the apparently unifying pathology of severe PH using genomics applied to lung tissue [122]. As illustrated in the color Figures, a lung with severe PH shows a range of ongoing vascular lesions, with distinct severities and cellular compositions.…”

Identification of candidate genes in scleroderma-related pulmonary arterial hypertension

“…Bull et al demonstrated that gene expression profiling of PBMCs efficiently discriminates between patients with PAH and normal volunteers and identifies PAH-specific genes (11,12). We therefore hypothesized that gene expression profiling of PBMCs from SSc patients with PAH can identify PAH-specific genes despite the presence of dysregulated immunity in these patients.…”

Peripheral blood gene expression profiling for cardiovascular disease assessment

“…Bull et al looked at the gene expression profiling of PBMCs to look for genetic signatures of pulmonary arterial hypertension (PAH). The gene expression profile of 16 patients with PAH showed 106 differentially expressed genes that distinguished between controls and PAH patients with 95-100% accuracy (P \ 0.002) (Bull et al 2004. However, within the PAH patients, unsupervised cluster analysis failed to show a genetic signature that reliably distinguished between secondary pulmonary arterial hypertension and idiopathic pulmonary arterial hypertension.…”