Erythroid-specific transcriptional changes in PBMCs from pulmonary hypertension patients.
| Autor: | Cheadle C; Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. ccheadl1@jhmi.edu, Berger AE, Mathai SC, Grigoryev DN, Watkins TN, Sugawara Y, Barkataki S, Fan J, Boorgula M, Hummers L, Zaiman AL, Girgis R, McDevitt MA, Johns RA, Wigley F, Barnes KC, Hassoun PM |
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| Jazyk: | angličtina |
| Zdroj: | PloS one [PLoS One] 2012; Vol. 7 (4), pp. e34951. Date of Electronic Publication: 2012 Apr 24. |
| DOI: | 10.1371/journal.pone.0034951 |
| Abstrakt: | Background: Gene expression profiling of peripheral blood mononuclear cells (PBMCs) is a powerful tool for the identification of surrogate markers involved in disease processes. The hypothesis tested in this study was that chronic exposure of PBMCs to a hypertensive environment in remodeled pulmonary vessels would be reflected by specific transcriptional changes in these cells. Methodology/principal Findings: The transcript profiles of PBMCs from 30 idiopathic pulmonary arterial hypertension patients (IPAH), 19 patients with systemic sclerosis without pulmonary hypertension (SSc), 42 scleroderma-associated pulmonary arterial hypertensio patients (SSc-PAH), and 8 patients with SSc complicated by interstitial lung disease and pulmonary hypertension (SSc-PH-ILD) were compared to the gene expression profiles of PBMCs from 41 healthy individuals. Multiple gene expression signatures were identified which could distinguish various disease groups from controls. One of these signatures, specific for erythrocyte maturation, is enriched specifically in patients with PH. This association was validated in multiple published datasets. The erythropoiesis signature was strongly correlated with hemodynamic measures of increasing disease severity in IPAH patients. No significant correlation of the same type was noted for SSc-PAH patients, this despite a clear signature enrichment within this group overall. These findings suggest an association of the erythropoiesis signature in PBMCs from patients with PH with a variable presentation among different subtypes of disease. Conclusions/significance: In PH, the expansion of immature red blood cell precursors may constitute a response to the increasingly hypoxic conditions prevalent in this syndrome. A correlation of this erythrocyte signature with more severe hypertension cases may provide an important biomarker of disease progression. |
| Databáze: | MEDLINE |
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