title: Gene expression profiling reveals potential prognostic biomarkers associated with the progression of heart failure.
abstract: BACKGROUND
  Heart failure (HF) is the most common cause of morbidity and mortality in developed countries. Here, we identify biologically relevant transcripts that are significantly altered in the early phase of myocardial infarction and are associated with the development of post-myocardial infarction HF.
  
  
  METHODS
  We collected peripheral blood samples from patients with ST-segment elevation myocardial infarction (STEMI): n = 111 and n = 41 patients from the study and validation groups, respectively. Control groups comprised patients with a stable coronary artery disease and without a history of myocardial infarction. Based on plasma NT-proBNP level and left ventricular ejection fraction parameters the STEMI patients were divided into HF and non-HF groups. Microarrays were used to analyze mRNA levels in peripheral blood mononuclear cells (PBMCs) isolated from the study group at four time points and control group. Microarray results were validated by RT-qPCR using whole blood RNA from the validation group.
  
  
  RESULTS
  Samples from the first three time points (admission, discharge, and 1 month after AMI) were compared with the samples from the same patients collected 6 months after AMI (stable phase) and with the control group. The greatest differences in transcriptional profiles were observed on admission and they gradually stabilized during the follow-up. We have also identified a set of genes the expression of which on the first day of STEMI differed significantly between patients who developed HF after 6 months of observation and those who did not. RNASE1, FMN1, and JDP2 were selected for further analysis and their early up-regulation was confirmed in HF patients from both the study and validation groups. Significant correlations were found between expression levels of these biomarkers and clinical parameters. The receiver operating characteristic (ROC) curves indicated a good prognostic value of the genes chosen.
  
  
  CONCLUSIONS
  This study demonstrates an altered gene expression profile in PBMCs during acute myocardial infarction and through the follow-up. The identified gene expression changes at the early phase of STEMI that differentiated the patients who developed HF from those who did not could serve as a convenient tool contributing to the prognosis of heart failure.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Maciejak
authors.affiliation: 1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland ; Department of Cardiology and Internal Diseases, Military Institute of Medicine, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Kiliszek
authors.affiliation: 1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Michalak
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Tulacz
authors.affiliation: 1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Opolski
authors.affiliation: Department of Cardiac Surgery, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Matlak
authors.affiliation: Department of Invasive Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Dobrzycki
authors.affiliation: Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, Warsaw, Poland ; 1st Medical Faculty, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Segiet
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Gora
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Burzynska