Blood Signature of Pre-Heart Failure: A Microarrays Study

Smih, Fatima; Desmoulin, Franck; Berry, Matthieu; Turkieh, Annie; Harmancey, Romain; Iacovoni, Jason S.; Trouillet, Charlotte; Delmas, Clément; Pathak, Atul; Lairez, Olivier; Koukoui, François; Massabuau, P; Ferrières, Jean; Galinier, Michel; Rouet, Philippe

doi:10.1371/journal.pone.0020414

Cited by 22 publications

(20 citation statements)

References 34 publications

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“…Using PBMC transcriptome as biomarkers in patients with decompensated heart failure, transcripts related to inflammation and oxidative stress were expressed in abundance, including NFκB, MCP-1, TNF-α and TGF-β 1 (3–9). It has recently been suggested PBMC gene expression profiling may identify the preclinical stage of systolic heart failure (21) and upregulated PBMC gene network may provide a molecular signature distinguishing patients with heart failure from healthy controls (8). …”

Section: Discussionmentioning

confidence: 99%

“…In searching for a surrogate tissue, tracking the prooxidant/proinflammatory pathway to cardiomyocyte necrosis, we turned to peripheral blood mononuclear cells (PBMC; lymphocytes and monocytes), as integral to cellular/molecular mechanisms of tissue repair and cardiac pathology (18). Our rationale in targeting PBMC as a putative surrogate was based on the following: i ) the gene expression profile of multiple tissues is shared with PBMC (19); ii ) PBMC are integral to the neuroendocrine-immune system interface invoked during stressor states with the microarray profiling of their transcriptome used to identify molecular signaling pathways; iii ) PBMC activation reveals molecular signatures in chronic heart failure and predicts its severity (5–9,20,21); iv ) our previous studies identified the activation of PBMC transcriptome at preclinical (wk 1) and pathologic (wk 4) stages of aldosterone/salt treatment (ALDOST) in rats (22,23); and v ) the availability of PBMC for clinical interrogation as a noninvasive target which could be monitored serially during the course of neurohormonal activation to predict risk and pathology prior to and with its appearance and response to intervention.…”

Section: Introductionmentioning

confidence: 99%

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Gene Expression Profiles of Peripheral Blood Mononuclear Cells Reveal Transcriptional Signatures as Novel Biomarkers of Cardiac Remodeling in Rats With Aldosteronism and Hypertensive Heart Disease

Gerling

Ahokas

Kamalov

et al. 2013

JACC: Heart Failure

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Objectives In searching for a noninvasive surrogate tissue having mimicry with the prooxidant/-proinflammatory hypertensive heart disease (HHD) phenotype, we turned to peripheral blood mononuclear cells (PBMC). We tested whether iterations in [Ca2+]i, [Zn2+]i and oxidative stress in cardiomyocytes and PBMC would complement each other eliciting similar shifts in gene expression profiles in these tissues demonstrable during preclinical (wk 1) and pathologic (wk 4) stages of aldosterone/salt treatment (ALDOST). Background Inappropriate neurohormonal activation contributes to pathologic remodeling of myocardium in HHD associated with aldosteronism. In rats receiving chronic ALDOST, evidence of reparative fibrosis replacing necrotic cardiomyocytes and coronary vasculopathy appears at wk 4 associated with the induction of oxidative stress by mitochondria that overwhelms endogenous, largely Zn2+-based, antioxidant defenses. Biomarker-guided prediction of risk prior to the appearance of cardiac pathology would prove invaluable. Methods In PBMC and cardiomyocytes, quantitation of cytoplasmic free Ca2+ and Zn2+, H2O2 and 8-iosprostane levels, as well as isolation of RNA and gene expression, together with statistical and clustering analyses, and confirmation of genes by in situ hybridization and RT-PCR, were performed. Results Compared to controls, at wk 1 and 4 ALDOST, we found comparable: increments in [Ca2+]i, [Zn2+]i and 8-isoprotane coupled to increased H2O2 production in cardiac mitochondria and PBMC, together with the common networks of expression profiles dominated by genes involved in oxidative stress, inflammation and repair. These included three central Ingenuity pathway-linked genes: p38MAPK, a stress-responsive protein; NFκB, a redox-sensitive transcription factor and a proinflammatory cascade it regulates; and TGF-β1, a fibrogenic cytokine involved in tissue repair. Conclusions Significant overlapping demonstrated in the molecular mimicry of PBMC and cardiomyocytes during preclinical and pathologic stages of ALDOST implicates that transcriptional signatures of PBMC may serve as early noninvasive and novel sentinels predictive of impending pathologic remodeling in HHD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gene Expression Profiles of Peripheral Blood Mononuclear Cells Reveal Transcriptional Signatures as Novel Biomarkers of Cardiac Remodeling in Rats With Aldosteronism and Hypertensive Heart Disease

Gerling

Ahokas

Kamalov

et al. 2013

JACC: Heart Failure

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“…Global changes in blood transcript abundance have also been investigated in patients with cardiovascular diseases, including heart diseases (e.g. atrial fibrillation [61] and heart failure [62]), hypertension (e.g. [63]) and stroke, with 21 studies published to date that have characterized blood transcript signatures associated with stroke and in some cases found to be predictive of recovery or complications (e.g.…”

Section: Blood Transcriptome Profiling Studies In Health and Diseasementioning

confidence: 99%

Assessment of immune status using blood transcriptomics and potential implications for global health

Chaussabel¹

2015

Seminars in Immunology

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The immune system plays a key role in health maintenance and pathogenesis of a wide range of diseases. Leukocytes that are present in the blood convey valuable information about the status of the immune system. Blood transcriptomics, which consists in profiling blood transcript abundance on genome-wide scales, has gained in popularity over the past several years. Indeed, practicality and simplicity largely makes up for what this approach may lack in terms of cell population-level resolution. An extensive survey of the literature reveals increasingly widespread use across virtually all fields of medicine as well as across a number of different animal species, including model organisms but also animals of economical importance. Dissemination across such a wide range of disciplines holds the promise of adding a new perspective, breadth or context, to the considerable depth afforded by whole genome profiling of blood transcript abundance. Indeed, it is only through such contextualization that a truly global perspective will be gained from the use of systems approaches. Also discussed are opportunities that may arise for the fields of immunology and medicine from using blood transcriptomics as a common denominator for developing interactions and cooperation across fields of research that have traditionally been and largely remain compartmentalized. Finally, an argument is made for building immunology research capacity using blood transcriptomics platforms in low-resource and high-disease burden settings.

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“…The discovery and the first local validation cohorts were constituted with 336 patients (224 controls vs 112 HF cases) selected from the IBLOMAVED cohort [10] who were recruited in the cardiology and pulmology department at the University Hospital Toulouse, France (Fig. 1A) using simple random sampling.…”

Section: Patientsmentioning

confidence: 99%

Proteomics analysis reveals IGFBP2 as a candidate diagnostic biomarker for heart failure

Berry

Galinier

Delmas

et al. 2015

IJC Metabolic & Endocrine

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Background: Diagnostic biomarkers for heart failure (HF) such as the natriuretic peptides (NPs) are widely used but have limitations. Innovative biomarkers could provide improved diagnostic performance. Methods: We launched a prospective case-control proteomic study and investigated for polypeptides specific to HF through a capillary electrophoresis-mass spectrometry (CE-MS) proteomic analysis. The putative biomarker was identified by Orbitrap liquid chromatography-MS, validated by western blot, then by ELISA using plasmas from multicentric international cohorts. A rat model of HF was tested for biomarker expression levels. Results: We identified insulin like growth factor binding protein 2 (IGFBP2) as a new diagnostic biomarker for HF with a high sensitivity and specificity (AUC = 0.93; 95% CI, 0.89-0.96; p b 0.0001) in the local cohort and IGFBP2 levels provided an AUC of 0.943 (95% CI, 0.860-1.026) which gave a 87 % sensitivity in AHF and 90 % specificity at the cut off value previously determined in the discovery cohort, i.e. 556 ng/ml. ROC curve analysis of IGFBP2 and NTproBNP showed an AUC of 0.784 (95% CI, 0.744-0.820) for IGFBP2 and a significantly higher AUC of 0.927 (95% CI, 0.900-0.949) for NT-proBNP, p b 0.0001 in a Dutch cohort. In this cohort, the optimal cut off value for IGFBP2 gave a sensibility of 71% (95% CI, 66-76) and a specificity of 75% (95% CI, 65-83). Conclusion: IGFBP2 is a new biomarker to diagnose HF which could be used to provide additional information to the NPs. Animals models will help in the evaluation of the putative IGFBP2 regulated mechanisms in HF. Clinical Trial Registration: ClinicalTrials.gov NCT01024049.

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Blood Signature of Pre-Heart Failure: A Microarrays Study

Cited by 22 publications

References 34 publications

Gene Expression Profiles of Peripheral Blood Mononuclear Cells Reveal Transcriptional Signatures as Novel Biomarkers of Cardiac Remodeling in Rats With Aldosteronism and Hypertensive Heart Disease

Gene Expression Profiles of Peripheral Blood Mononuclear Cells Reveal Transcriptional Signatures as Novel Biomarkers of Cardiac Remodeling in Rats With Aldosteronism and Hypertensive Heart Disease

Assessment of immune status using blood transcriptomics and potential implications for global health

Proteomics analysis reveals IGFBP2 as a candidate diagnostic biomarker for heart failure

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