Limited Systemic Sclerosis Patients with Pulmonary Arterial Hypertension Show Biomarkers of Inflammation and Vascular Injury

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dc.contributor.author Pendergrass, Sarah A. en_US
dc.contributor.author Hayes, Everett en_US
dc.contributor.author Farina, Giuseppina en_US
dc.contributor.author Lemaire, Raphael en_US
dc.contributor.author Farber, Harrison W. en_US
dc.contributor.author Whitfield, Michael L. en_US
dc.contributor.author Lafyatis, Robert en_US
dc.date.accessioned 2012-01-09T21:04:07Z
dc.date.available 2012-01-09T21:04:07Z
dc.date.issued 2010-8-17 en_US
dc.identifier.citation Pendergrass, Sarah A., Everett Hayes, Giuseppina Farina, Raphael Lemaire, Harrison W. Farber, Michael L. Whitfield, Robert Lafyatis. "Limited Systemic Sclerosis Patients with Pulmonary Arterial Hypertension Show Biomarkers of Inflammation and Vascular Injury" PLoS ONE 5(8): e12106. (2010) en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://hdl.handle.net/2144/2982
dc.description.abstract BACKGROUND. Pulmonary arterial hypertension (PAH) is a common complication for individuals with limited systemic sclerosis (lSSc). The identification and characterization of biomarkers for lSSc-PAH should lead to less invasive screening, a better understanding of pathogenesis, and improved treatment. METHODS AND FINDINGS. Forty-nine PBMC samples were obtained from 21 lSSc subjects without PAH (lSSc-noPAH), 15 lSSc subjects with PAH (lSSc-PAH), and 10 healthy controls; three subjects provided PBMCs one year later. Genome-wide gene expression was measured for each sample. The levels of 89 cytokines were measured in serum from a subset of subjects by Multi-Analyte Profiling (MAP) immunoassays. Gene expression clearly distinguished lSSc samples from healthy controls, and separated lSSc-PAH from lSSc-NoPAH patients. Real-time quantitative PCR confirmed increased expression of 9 genes (ICAM1, IFNGR1, IL1B, IL13Ra1, JAK2, AIF1, CCR1, ALAS2, TIMP2) in lSSc-PAH patients. Increased circulating cytokine levels of inflammatory mediators such as TNF-alpha, IL1-beta, ICAM-1, and IL-6, and markers of vascular injury such as VCAM-1, VEGF, and von Willebrand Factor were found in lSSc-PAH subjects. CONCLUSIONS AND SIGNIFICANCE. The gene expression and cytokine profiles of lSSc-PAH patients suggest the presence of activated monocytes, and show markers of vascular injury and inflammation. These genes and factors could serve as biomarkers of PAH involvement in lSSc. en_US
dc.description.sponsorship Actelion Pharmaceuticals Ltd; Arthritis Foundation (Hulda Irene Duggan Arthritis Investigator Award, T32 AR007575-11) en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.rights Pendergrass et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_US
dc.title Limited Systemic Sclerosis Patients with Pulmonary Arterial Hypertension Show Biomarkers of Inflammation and Vascular Injury en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pone.0012106 en_US
dc.identifier.pubmedid 20808962 en_US
dc.identifier.pmcid 2923145 en_US

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