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Gene expression profiling reveals potential prognostic biomarkers associated with the progression of heart failure
Agata Maciejak1, Marek Kiliszek2, Marcin Michalak3
1Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
Insights
Early detection of heart failure (HF) after myocardial infarction is crucial. This study identified specific gene expression changes in peripheral blood mononuclear cells (PBMCs) that predict HF development, offering a potential new diagnostic tool.
Area of Science:
- Cardiovascular Biology
- Molecular Diagnostics
- Genomics
Background:
- Heart failure (HF) is a leading cause of death in developed nations.
- Identifying early indicators of HF post-myocardial infarction (MI) is critical for patient outcomes.
- Understanding transcriptional alterations in early MI can reveal pathways leading to HF.
Purpose of the Study:
- To identify early, biologically relevant transcripts altered during acute myocardial infarction (MI).
- To associate specific gene expression profiles with the subsequent development of heart failure (HF) post-MI.
- To evaluate the potential of identified biomarkers for predicting HF in STEMI patients.
Main Methods:
- Peripheral blood samples were collected from ST-segment elevation myocardial infarction (STEMI) patients and controls.
- Microarrays analyzed mRNA levels in peripheral blood mononuclear cells (PBMCs) at multiple time points post-MI.
- RT-qPCR validated microarray findings in an independent patient cohort.
- STEMI patients were stratified into HF and non-HF groups based on NT-proBNP and ejection fraction.
Main Results:
- Significant differences in transcriptional profiles were observed early after STEMI, stabilizing over time.
- A distinct set of genes, including RNASE1, FMN1, and JDP2, showed significantly different expression on day one between patients who did and did not develop HF.
- Early upregulation of RNASE1, FMN1, and JDP2 was confirmed in HF patients, correlating with clinical parameters.
- Receiver operating characteristic (ROC) analysis indicated a good prognostic value for these identified genes.
Conclusions:
- Gene expression profiles in PBMCs are altered during acute MI and its follow-up period.
- Early-phase STEMI gene expression changes can differentiate patients who will develop HF.
- The identified gene expression markers may serve as a valuable tool for early heart failure prognosis.
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.
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