Plasma microRNAs are associated with atrial fibrillation and change after catheter ablation (the miRhythm study)
Introduction
Atrial fibrillation (AF) is an important cardiovascular health problem with major adverse health consequences.1 The prevalence of AF is 5.2 million in the United States today and is predicted to rise to 12.1 million by 2030.2 Clinical risk scores show modest predictive ability at identifying individuals at risk for AF, but few robust AF biomarkers exist.3
MicroRNAs (miRNAs) are a class of RNA species with gene regulatory functions. Tissue levels of miRNAs have been associated with processes underlying cardiovascular diseases,4, 5, 6 including cardiac electrical remodeling (miR-328)7, 8, 9, 10 and structural remodeling (miR-21).11, 12, 13 miRNAs can be exported by cardiomyocytes14 and fibroblasts and are present in the circulation,15, 16 but little is known about the source and significance of circulating miRNAs, particularly as they relate to arrhythmias.17
Despite reports implicating miRNAs as determinants of susceptibility to AF under experimental conditions,18, 19, 20 few studies have examined the relationships between circulating miRNAs and AF in humans.9, 19 In a previous study, we showed that whole-blood levels of miR-328, an miRNA associated with L-type Ca2+ channel density and AF susceptibility,21 was associated with prevalent AF.9, 22, 23 We hypothesized that plasma miRNAs would provide a clear window into cardiac gene regulation in AF and after ablation. We sought to explore these hypotheses by profiling expression of 86 miRNAs in plasma and atrial tissue in a prospectively recruited cohort.
Section snippets
Study sample
The miRhythm study is an ongoing, prospective study of AF and its gene regulatory mechanisms. Study participants include individuals with and without AF who presented to the University of Massachusetts Medical Center (UMMC) for evaluation or treatment between April 2011 and January 2014. To date, investigators have enrolled 453 individuals presenting to the UMMC, including 227 presenting for an ablation procedure, 114 presenting for surgery, and 112 presenting for cardiovascular evaluation. For
Results
The characteristics of the miRhythm participants who composed the study sample are given in Table 1. The clinical and surgical characteristics of the subsample of miRhythm participants who donated atrial tissue and plasma are given in Table 2.
The overall sample included middle-aged and older adults with a modest burden of cardiovascular risk factors. Participants with AF were more likely to be men and have higher body mass as well as echocardiographic left atrial volume indices. Study
Discussion
In our prospective study of 211 participants (Table 1) powered to detect subtle differences in plasma miRNA expression, we observed that miRs-21 and 150 were differentially expressed in the plasma of patients with preexisting AF and that associations persisted after adjustment for factors known to influence circulating miRNA profiles and susceptibility to AF. We also observed that miR-21 expression was lower in atrial tissue isolated from participants with AF and that miRs-21 and 150 increased
Conclusion
We observed strong associations between plasma levels of miRs-21 and 150, 2 miRNAs expressed in cardiac tissue and linked to atrial remodeling, with AF. Our findings support the hypothesis that circulating miRNAs provide key insights into cardiac gene regulation and implicate miRs-21 and 150 as markers of susceptibility to AF.
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2021, Ageing Research ReviewsMicroRNAs: New contributors to mechano-electric coupling and atrial fibrillation
2021, Progress in Biophysics and Molecular BiologyCitation Excerpt :In addition to AF diagnosis, miR biomarkers may provide information about the specific atrial cardiomyopathy and remodeling type underlying AF, with implications for prognosis and patient-tailored therapy (Sardu et al., 2015). For instance, miR-150 and miR-155 were suggested as prognostic biomarkers for predicting catheter ablation (McManus et al., 2015) and cardioversion therapy outcomes (Sardu et al., 2015), respectively. Of note, miR-155 levels displayed a positive correlation with left atrial diameter and inflammatory markers, but not with ejection fraction values, which may suggest a specific relation of this biomarker with a stretch-induced atrial remodeling state (Zhang et al., 2019).
MicroRNAs and Cardiovascular Disease Risk
2024, Current Cardiology ReportsPathophysiology and clinical relevance of atrial myopathy
2024, Basic Research in Cardiology
This study was supported by Grants 1U01HL105268-01 and KL2RR031981 to Dr. McManus; N01-HC 25195, 6R01-NS 17950, RFA-HL-12-008, and 1R01 HL64753 to Dr. Freedman; R01 HL087201A to Drs. Freedman and Tanriverdi; and R01 HL076784 and 1 R01 AG028321 to Dr. Benjamin from the National Heart, Lung, Blood Institute, National Institutes of Health.