Comparison of Whole Blood and Peripheral Blood Mononuclear Cell Gene Expression for Evaluation of the Perioperative Inflammatory Response in Patients with Advanced Heart Failure

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Galyna,Cadeiras,Martin,Wisniewski,Nicholas,Maque,J Bondar (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Background: Heart failure (HF) prevalence is increasing in the United States.Mechanical Circulatory Support (MCS) therapy is an option for Advanced HF(AdHF) patients. Perioperatively, multiorgan dysfunction (MOD) is linked to theeffects of device implantation, augmented by preexisting HF. Early recognition ofMOD allows for better diagnosis, treatment, and risk prediction. Gene expressionprofiling (GEP) was used to evaluate clinical phenotypes of peripheral bloodmononuclear cells (PBMC) transcriptomes obtained from patients" blood samples.Whole blood (WB) samples are clinically more feasible, but their performance incomparison to PBMC samples has not been determined.Methods: We collected blood samples from 31 HF patients (57¡15 years old)undergoing cardiothoracic surgery and 7 healthy age-matched controls, between2010 and 2011, at a single institution. WB and PBMC samples were collected at asingle timepoint postoperatively (median day 8 postoperatively) (25--75% IQR 7--14days) and subjected to Illumina single color Human BeadChip HT12 v4 wholegenome expression array analysis. The Sequential Organ Failure Assessment(SOFA) score was used to characterize the severity of MOD into low (# 4 points),intermediate (5--11), and high ($ 12) risk categories correlating with GEP.Results: Results indicate that the direction of change in GEP of individuals withMOD as compared to controls is similar when determined from PBMC versus WB.The main enriched terms by Gene Ontology (GO) analysis included those involvedin the inflammatory response, apoptosis, and other stress response relatedpathways. The data revealed 35 significant GO categories and 26 pathwaysoverlapping between PBMC and WB. Additionally, class prediction using machinelearning tools demonstrated that the subset of significant genes shared by PBMCand WB are sufficient to train as a predictor separating the SOFA groups.Conclusion: GEP analysis of WB has the potential to become a clinical tool forimmune-monitoring in patients with MOD

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Language: English

Date: 2014

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