Abstract
Background: The current gold standard biomarker for myocardial infarction (MI), cardiac troponin (cTn), is recognized for its high sensitivity and organ specificity; however, it lacks diagnostic specificity. Numerous studies have introduced circulating microRNAs as potential biomarkers for MI. This study investigates the MI-specificity of these serum microRNAs by investigating myocardial stress/injury due to strenuous exercise. Methods: MicroRNA biomarkers were retrieved by comprehensive review of 109 publications on diagnostic serum microRNAs for MI. MicroRNA levels were first measured by next-generation sequencing in pooled sera from runners (n = 46) before and after conducting a full competitive marathon. Hereafter, reverse transcription quantitative real-time PCR (qPCR) of 10 selected serum microRNAs in 210 marathon runners was performed (>10,000 qPCR measurements). Results: 27 potential diagnostic microRNA for MI were retrieved by the literature review. Eight microRNAs (miR-1-3p, miR-21-5p, miR-26a-5p, miR-122-5p, miR-133a-3p, miR-142-5p, miR-191-5p, miR-486-3p) showed positive correlations with cTnT in marathon runners, whereas two miRNAs (miR-134-5p and miR-499a-5p) showed no correlations. Upregulation of miR-133a-3p (p = 0.03) and miR-142-5p (p = 0.01) went along with elevated cTnT after marathon. Conclusion: Some MI-associated microRNAs (e.g., miR-133a-3p and miR-142-5p) have similar kinetics under strenuous exercise and MI as compared to cTnT, which suggests that their diagnostic specificity could be limited. In contrast, several MI-associated microRNAs (miR-26a-5p, miR-134-5p, miR-191-5p) showed different release behavior; hence, combining cTnT with these microRNAs within a multi-marker strategy may add diagnostic accuracy in MI.
Highlights
Myocardial infarction (MI) is a relevant world-wide medical burden, which is associated with high mortality [1] and reduced quality of life in many survivors [2]
The current gold standard biomarker for myocardial infarction (MI) is measurement of cardiac troponins, which is highly sensitive for myocardial injury and highly specific for cardiomyocytes [3,4]
19 original articles were used to extract MI miRNAs that were measured in serum (Figure 1)
Summary
Myocardial infarction (MI) is a relevant world-wide medical burden, which is associated with high mortality [1] and reduced quality of life in many survivors [2]. The current gold standard biomarker for MI is measurement of cardiac troponins (cTn), which is highly sensitive for myocardial injury and highly specific for cardiomyocytes [3,4]. Due to cTn’s lack of diagnostic specificity, the accurate selection of patients with MI remains challenging This is challenging in patients who experience corresponding clinical symptoms during or shortly after strenuous exercise. The current gold standard biomarker for myocardial infarction (MI), cardiac troponin (cTn), is recognized for its high sensitivity and organ specificity; it lacks diagnostic specificity. This study investigates the MI-specificity of these serum microRNAs by investigating myocardial stress/injury due to strenuous exercise. Conclusion: Some MI-associated microRNAs (e.g., miR-133a-3p and miR-142-5p) have similar kinetics under strenuous exercise and MI as compared to cTnT, which suggests that their diagnostic specificity could be limited. Several MI-associated microRNAs (miR-26a-5p, miR-134-5p, miR-191-5p) showed different release behavior; combining cTnT with these microRNAs within a multi-marker strategy may add diagnostic accuracy in MI
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