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Gene expression profiles in peripheral blood mononuclear cells of chronic heart failure patients
Claudia Cappuzzello1, Monica Napolitano, Diego Arcelli
1Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata IRCCS, Rome.
Insights
Researchers identified key gene expression patterns in peripheral blood mononuclear cells (PBMCs) to find biomarkers for chronic heart failure (CHF). Chemokine receptor and early growth response genes were upregulated in CHF patients, with EGR1 distinguishing between ischemic and non-ischemic types.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Biomarker Discovery
Background:
- Chronic heart failure (CHF) poses a significant health burden, necessitating novel diagnostic and prognostic tools.
- Peripheral blood mononuclear cells (PBMCs) offer a readily accessible source for identifying molecular signatures of disease.
- Distinguishing between ischemic (ICM) and non-ischemic dilated (NIDCM) cardiomyopathy is crucial for targeted treatment.
Purpose of the Study:
- To identify gene expression biomarkers for chronic heart failure (CHF) in PBMCs.
- To differentiate molecular signatures between ICM and NIDCM patient groups.
- To validate potential CHF biomarkers using quantitative methods.
Main Methods:
- PBMC gene expression profiling using Affymetrix microarrays in CHF patients (ICM and NIDCM) and controls.
- Bioinformatic analyses including Gene Ontology (GO), Prediction Analysis of Microarrays (PAM), and Significance Analysis of Microarrays (SAM).
- Validation of candidate biomarkers via quantitative real-time polymerase chain reaction (qRT-PCR).
Main Results:
- A distinct gene expression profile was identified, differentiating CHF patients from healthy controls.
- Upregulation of chemokine receptor (CCR2, CX(3)CR1) and early growth response (EGR1, 2, 3) gene families in CHF patients.
- Early Growth Response 1 (EGR1) expression levels demonstrated the ability to discriminate between ICM and NIDCM.
Conclusions:
- This study presents the first large-scale gene expression analysis of CHF PBMCs, revealing a molecular signature.
- Chemokine receptor and EGR family members are identified as putative biomarkers for chronic heart failure.
- EGR1 serves as a potential biomarker for differentiating between ischemic and non-ischemic dilated cardiomyopathy.
Abstract:
The present study was aimed at identifying chronic heart failure (CHF) biomarkers from peripheral blood mononuclear cells (PBMCs) in patients with ischemic (ICM) and nonischemic dilated (NIDCM) cardiomyopathy. PBMC gene expression profiling was performed by Affymetrix in two patient groups, 1) ICM (n = 12) and 2) NIDCM (n = 12) New York Heart Association (NYHA) III/IV CHF patients, vs. 3) age- and sex-matched control subjects (n = 12). Extracted RNAs were then pooled and hybridized to a total of 11 microarrays. Gene ontology (GO) analysis separated gene profiling into functional classes. Prediction analysis of microarrays (PAM) and significance analysis of microarrays (SAM) were utilized in order to identify a molecular signature. Candidate markers were validated by quantitative real-time polymerase chain reaction. We identified a gene expression profiling that distinguished between CHF patients and control subjects. Interestingly, among the set of genes constituting the signature, chemokine receptor (CCR2, CX(3)CR1) and early growth response (EGR1, 2, 3) family members were found to be upregulated in CHF patients vs. control subjects and to be part of a gene network. Such findings were strengthened by the analysis of an additional 26 CHF patients (n = 14 ICM and n = 12 NIDCM), which yielded similar results. The present study represents the first large-scale gene expression analysis of CHF patient PBMCs that identified a molecular signature of CHF and putative biomarkers of CHF, i.e., chemokine receptor and EGR family members. Furthermore, EGR1 expression levels can discriminate between ICM and NIDCM CHF patients.
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