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Published on: September 15, 2018
Influence of microRNAs on iNOS expression in postmortem human infarction hearts
Verena Wilmes1, Luise Mildeberger1, Marcel A Verhoff1
1Institute of Legal Medicine, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
Abstract:
MicroRNAs (miRNAs) are important post-transcriptional regulators in several diseases, including cancer, immunologic and cardiovascular diseases. A growing list of miRNAs are dysregulated in cardiac arrhythmias, contractility diseases, myocardial infarction (MI), sudden cardiac death (SCD), chronic heart failure and hypertrophy. However, the exact regulatory pathways, through which miRNAs exert their effects are often unclear. In this study, we measured the expression patterns of miR-21, miR-939 and miR-30e in postmortem human MI. The aim of the study was to examine the influence of these miRNAs on cardiac inducible nitric oxide synthase (iNOS) mRNA levels. We measured iNOS mRNA and miRNA expression patterns by means of qPCR. Further we used correlation analyses to determine causality between miRNA expression and cardiac iNOS levels. iNOS mRNA, miR-21, miR-939 and miR-30e were significantly upregulated in infarcted and non-infarcted regions of postmortem human MI hearts in comparison to healthy controls. While miR-21 and miR-939 showed their strongest expression in infarcted regions, miR-30e peaked in the non-infarcted myocardium. Further, we found a significant correlation between miR-939 and iNOS expression levels in controls and infarcted regions. The results indicate, that miR-939 is a regulator of cardiac iNOS expression. However, a massive iNOS activation might exceed the capability of miR-939 to keep its expression in balance. miR-21 and miR-30e do not seem to influence cardiac iNOS levels in MI. Further studies are needed to evaluate downstream targets of these miRNAs and their signaling pathways to clarify their role in human MI.
Insights
MicroRNAs (miRNAs) regulate gene expression. In this study, miR-939 was found to correlate with cardiac inducible nitric oxide synthase (iNOS) mRNA in myocardial infarction (MI) hearts, suggesting a regulatory role.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are key post-transcriptional regulators implicated in various diseases, including cardiovascular conditions.
- Dysregulation of specific miRNAs is observed in conditions like myocardial infarction (MI), but their precise roles remain unclear.
Purpose of the Study:
- To investigate the expression patterns of miR-21, miR-939, and miR-30e in postmortem human MI hearts.
- To determine the influence of these miRNAs on cardiac inducible nitric oxide synthase (iNOS) mRNA levels.
Main Methods:
- Quantitative real-time PCR (qPCR) was used to measure iNOS mRNA and miRNA expression.
- Correlation analyses were performed to establish relationships between miRNA expression and cardiac iNOS levels.
Main Results:
- iNOS mRNA, miR-21, miR-939, and miR-30e were significantly upregulated in both infarcted and non-infarcted regions of MI hearts compared to controls.
- miR-939 expression showed a significant correlation with iNOS levels in control and infarcted heart tissues.
- miR-21 and miR-30e did not appear to influence cardiac iNOS levels in the context of MI.
Conclusions:
- miR-939 is identified as a potential regulator of cardiac iNOS expression in myocardial infarction.
- High iNOS activation may overwhelm miR-939's regulatory capacity.
- Further research is necessary to elucidate the downstream targets and signaling pathways of these miRNAs in human MI.
