Submitted on October 30, 2008
Revised on March 16, 2009
Accepted on March 30, 2009
GENE EXPRESSION PROFILES IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF CHRONIC HEART FAILURE PATIENTS
Claudia Cappuzzello1, Monica Napolitano2, Diego Arcelli3, Guido Melillo2, Roberta Melchionna2, Luca Di Vito4, Daniele Carlini2, Lorena Silvestri2, Salvatore Brugaletta4, Giovanna Liuzzo4, Filippo Crea4, and Maurizio C. Capogrossi5*
1 Centro Cardiologico Monzino-IRCCS
2 Istituto dermopatico dell'Immacolata-IRCCS
3 Istituto Dermopatico dell'Immacolata-IRCCS
4 Institute of Cardiology, Catholic University, Ospedale Gemelli, Rome Italy
5 Istituto Dermopatico dell'Immacolata-IRCCS, Rome Italy
* To whom correspondence should be addressed. E-mail: capogrossi{at}idi.it.
Aims: The present study aimed at identifying chronic heart failure (CHF) biomarkers from peripheral blood mononuclear cells (PBMCs) in patients with ischemic (ICM) and non-ischemic dilated (NIDCM) cardiomyopathy. Methods: PBMC gene expression profiling was performed, by Affymetrix, in two patients' groups: (1) ICM- (n=12) and (2) NIDCM- (n=12) NYHA III/IV CHF patients, vs (3) age- and gender-matched controls (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 qRT-PCR. Results: We identified a gene expression profiling that distinguished between CHF patients and controls. Interestingly, among the set of genes constituting the signature, chemokine receptor (CCR2, CX3CR1) and early growth factor (EGR1, 2, 3) family members were found to be upregulated in CHF patients vs controls, and to be part of a gene network. Such findings were strengthened by the analysis of additional 26 CHF patients (n=14 ICM and n=12 NIDCM), that yielded similar results. Conclusions: The present study represents the first large-scale gene expression analysis of CHF patients' 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.
