The role of microRNAs in the development, regulation, and treatment of atrial fibrillation
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MicroRNAs (miRNA)s regulate expression of genes involved in various processes including cardiac automaticity, conduction, excitability, and fibrosis and therefore may provide a diagnostic utility to identify high-risk patients for atrial fibrillation (AF). In this study, we tested the hypothesis that specific profiles of circulating miRNAs can identify patients with AF and can also help to identify patients at high risk of AF recurrence after ablation.
Two patient populations were studied: 140 AF cases (93 paroxysmal and 47 persistent) and 50 healthy controls, and 141 AF ablation cases with (n = 86) and without (n = 55) 1-year recurrence. Assessment of several previously identified AF-associated plasma miRNAs (21, 29a, 133a, 133b, 150, 328) was performed with TaqMan assays, using synthetic miRNAs as standards.
The AF cases compared to the healthy controls were older and were more often male and hypertensive. After multivariate adjustment, higher miRNA-21 levels significantly decreased the risk of AF (OR = 0.93 per fmol/μl (95% CI = 0.89–0.98, p = 0.007)). There were no significant differences in circulating miRNAs between the AF subtypes of persistent and paroxysmal. Among the AF ablation cases, miRNA-150 was lower for those with AF recurrences at 1 year (adjusted OR = 0.98 per 500,000 fmol/μl; 95% CI = 0.965, 0.998; p = 0.039).
Decreased circulating miRNA-21 is associated with AF, but not with AF subtypes, suggestive that molecular mechanisms responsible for the onset and progression of the AF may be different. Circulating miRNA-150 was significantly associated with a reduction in 1-year AF recurrence post ablation suggestive of adverse structural and electrical remodeling as recurrence mechanisms.
KeywordsAtrial fibrillation Ablation Outcomes Atrium MicroRNA Fibrosis Outcomes
The authors thank Matt Grover, Lizzy Stauder, and Johnny Thrang for their assistance with samples processing.
This study received funding from the Intermountain Research and Medical Foundation Grant.
Compliance with ethical standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was a retrospective design with stored serum used for analysis. All patients provided consent for the use of their serum and medical records for research purposes. The study was approved by the IRB.
Conflict of interest
Oxana Galenko: none
Victoria Jacobs: none
Stacey Knight: none
Madisyn Taylor: none
Michael J. Cutler: none
Joseph B. Muhlestein: none
John Carlquist: none
Kirk Knowlton: none
T. Jared Bunch: major, Boehringer Ingelheim research grant
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