TY - JOUR
T1 - Erythroid-specific transcriptional changes in PBMCs from pulmonary hypertension patients
AU - Cheadle, Chris
AU - Berger, Alan E.
AU - Mathai, Stephen C.
AU - Grigoryev, Dmitry N.
AU - Watkins, Tonya N.
AU - Sugawara, Yumiko
AU - Barkataki, Sangjucta
AU - Fan, Jinshui
AU - Boorgula, Meher
AU - Hummers, Laura
AU - Zaiman, Ari L.
AU - Girgis, Reda
AU - McDevitt, Michael A.
AU - Johns, Roger A.
AU - Wigley, Frederick
AU - Barnes, Kathleen C.
AU - Hassoun, Paul M.
PY - 2012/4/24
Y1 - 2012/4/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84860173596&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860173596&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0034951
DO - 10.1371/journal.pone.0034951
M3 - Article
C2 - 22545094
AN - SCOPUS:84860173596
VL - 7
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 4
M1 - e34951
ER -