Elevated serum microRNA 483-5p levels may predict patients at risk of post-operative atrial fibrillation

Abstract

OBJECTIVESPost-operative atrial fibrillation (POAF) is the commonest post-operative cardiac arrhythmia, affecting ∼1 in 3 patients undergoing coronary artery bypass grafting (CABG). Although its aetiology is complex, atrial substrate changes may pre-dispose to its onset. This study aims to ascertain the atrial microRNA signature of POAF and determine the potential for circulating microRNA as a pre-operative biomarker for this arrhythmia.METHODSThirty-four patients undergoing non-emergent, on-pump CABG were prospectively recruited. Right atrial biopsies were taken intra-operatively and snap frozen for RNA extraction. Plasma was obtained at 24 h pre-operatively and at 2 and 4 days post-operatively. POAF was defined by continuous Holter recording. Inter-group comparisons were performed using Student's t-test or analysis of variance as required. Receiver operating characteristic (ROC) analysis was used to determine the diagnostic accuracy of pre-operative serum miRNA as a POAF biomarker.RESULTSSixteen microRNAs were differentially expressed in the atrial myocardium of POAF patients when compared with those maintaining sinus rhythm. miR-208a was the most underexpressed [fold change (FC) = 2.458] and miR-483-5p the most overexpressed (FC = 1.804). miR-483-5p also demonstrated significant overexpression in the pre-operative serum of these patients, with ROC analysis demonstrating an overall predictive accuracy of 78%.CONCLUSIONSThis study provides the first description of atrial myocardial and circulating plasma microRNA in POAF patients. Our findings suggest POAF may be associated with pre-existing atrial substrate differences predisposing to arrhythmogenesis. Moreover, this study highlights the potential for miR-483-5p in biomarker development. Further work must now perform prospective, targeted validation of these results in a larger patient cohort.

Plasma Circular RNAs, Hsa_circRNA_025016, Predict Postoperative Atrial Fibrillation After Isolated Off‐Pump Coronary Artery Bypass Grafting

“…The study by Harling et al7 demonstrated that the levels of circulating and atrial tissue microRNAs are potential markers of PoAF. Other studies have found dysregulations of microRNAs in AF 10, 11.…”

“…PoAF is associated with significantly increased morbidity, mortality, and total treatment costs. 6 Although potential biomarkers of PoAF, such as mtDNA copy numbers and microRNAs, 7,8 have been actively researched, the diagnostic use of plasma circRNAs for PoAF has never been investigated. Our study screened the plasma circRNAs expression profiles (13 617 circRNAs) of patients with and without PoAF.…”

Molecular Mechanisms, Diagnostic Aspects and Therapeutic Opportunities of Micro Ribonucleic Acids in Atrial Fibrillation

“…Therefore, circulating miRNAs could serve as potential biomarkers for early identification of proarrhythmogenic substrate for AF. This might be of considerable interest especially in patients with subclinical AF [3,4]. Furthermore, targeting miRNAs could be a promising therapeutic strategy in the management of AF.…”

Micro RNAs in Cardiac Surgery: Novel Molecular Signatures!

“…The and the overexpression of miR-483-5p in the right atrial tissue of patients who experience postoperative atrial fibrillation after coronary artery bypass grafting. 2 Specifically, low-circulating baseline miR-21 plasma levels have been revealed as predictors of cardiac surgeryÀassociated acute kidney injury. 3 A few initial studies also have characterized the role of miR-1, miR-133a, and miR-223 in regulating IRI and systemic inflammatory response after bypass in coronary artery bypass grafting surgery patients.…”