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Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease
Published on: July 3, 2018
A translational study of circulating cell-free microRNA-1 in acute myocardial infarction
Yunhui Cheng1, Ning Tan, Jian Yang
1RNA and Cardiovascular Research Laboratory, Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07101, USA.
Abstract:
miRNAs (microRNAs) participate in many diseases including cardiovascular disease. In contrast with our original hypothesis, miRNAs exist in circulating blood and are relatively stable due to binding with other materials. The aim of the present translational study is to establish a method of determining the absolute amount of an miRNA in blood and to determine the potential applications of circulating cell-free miR-1 (microRNA-1) in AMI (acute myocardial infarction). The results revealed that miR-1 is the most abundant miRNA in the heart and is also a heart- and muscle-specific miRNA. In a cardiac cell necrosis model induced by Triton X-100 in vitro, we found that cardiac miR-1 can be released into the culture medium and is stable at least for 24 h. In a rat model of AMI induced by coronary ligation, we found that serum miR-1 is quickly increased after AMI with a peak at 6 h, in which an increase in miR-1 of over 200-fold was demonstrated. The miR-1 level returned to basal levels at 3 days after AMI. Moreover, the serum miR-1 level in rats with AMI had a strong positive correlation with myocardial infarct size. To verify further the relationship between myocardial size and miR-1 level, an IP (ischaemic preconditioning) model was used. The results showed that IP significantly reduced circulating miR-1 levels and myocardial infract size induced by I/R (ischaemia/reperfusion) injury. Finally, the levels of circulating cell-free miR-1 were significantly increased in patients with AMI and had a positive correlation with serum CK-MB (creatine kinase-MB) levels. In conclusion, the results suggest that serum miR-1 could be a novel sensitive diagnostic biomarker for AMI.
Insights
Circulating cell-free microRNA-1 (miR-1) shows potential as a sensitive biomarker for acute myocardial infarction (AMI). Studies demonstrate increased miR-1 levels in blood following AMI, correlating with infarct size, suggesting diagnostic utility.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiology
Background:
- MicroRNAs (miRNAs) are implicated in various diseases, including cardiovascular conditions.
- Contrary to initial hypotheses, circulating miRNAs are found in blood and exhibit stability.
- This study focuses on quantifying circulating cell-free miRNAs and their application in diagnosing acute myocardial infarction (AMI).
Purpose of the Study:
- To develop a method for determining the absolute quantity of miRNAs in blood.
- To investigate the potential of circulating cell-free microRNA-1 (miR-1) as a biomarker for AMI.
Main Methods:
- Establishment of a quantitative method for circulating cell-free miRNA analysis.
- In vitro cardiac cell necrosis model (Triton X-100) to assess miR-1 release and stability.
- In vivo rat model of AMI induced by coronary ligation.
- Ischaemic preconditioning (IP) model to evaluate the relationship between myocardial size and miR-1 levels.
- Analysis of circulating miR-1 levels in human patients diagnosed with AMI.
Main Results:
- miR-1 is identified as the most abundant, heart- and muscle-specific miRNA.
- Cardiac miR-1 is released into the medium and remains stable for at least 24 hours in vitro.
- In a rat AMI model, serum miR-1 increased over 200-fold, peaking at 6 hours post-ligation and returning to baseline by 3 days.
- Serum miR-1 levels positively correlated with myocardial infarct size in rats.
- Ischaemic preconditioning reduced both circulating miR-1 levels and infarct size.
- Significantly elevated circulating cell-free miR-1 levels were observed in human AMI patients, correlating with serum CK-MB levels.
Conclusions:
- Serum miR-1 is a heart- and muscle-specific miRNA that is released from damaged cardiac tissue.
- Circulating cell-free miR-1 levels increase rapidly and significantly following AMI.
- Serum miR-1 demonstrates potential as a novel and sensitive diagnostic biomarker for AMI.
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