Abstract
BackgroundHeart 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.MethodsWe 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.ResultsSamples 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-015-0149-z) contains supplementary material, which is available to authorized users.
Highlights
Heart failure (HF) is the most common cause of morbidity and mortality in developed countries
Significant differences between the two groups were observed for two parameters: hypercholesterolemia was significantly more common (P
We further examined the changes in the gene expression profiles unique to patients who developed HF after Acute myocardial infarction (AMI) and identified potential prognostic biomarkers associated with the post-infarction left ventricular (LV) remodeling
Summary
Heart failure (HF) is the most common cause of morbidity and mortality in developed countries. Genome-wide gene expression profiling is an extensively used strategy for discovering new potential biomarkers for diagnosis/prediction of disease severity [1,2] and identification of novel drug targets [3]. Coronary heart disease (CHD) is one of the major causes of heart failure (HF), the predominant cause of morbidity and mortality in developed countries. While advances in the management of HF have improved patient outcomes, it remains the leading hospital admission diagnosis in elderly patients and carries a 5-year mortality rate as high as 50% [6]. The HF prevalence in the general population in the developed countries is estimated to be in the range of 0.4% to 2% [7]. It can be assumed that 6.5 to 10 million
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