Abstract
BackgroundStructural changes of the left and right atria associated with atrial fibrillation (AF) in mitral stenosis (MS) patients are well known, and alterations in microRNA (miRNA) expression profiles of the right atria have also been investigated. However, miRNA changes in the left atria still require delineation. This study evaluated alterations in miRNA expression profiles of left atrial tissues from MS patients with AF relative to those with normal sinus rhythm (NSR).MethodsSample tissues from left atrial appendages were obtained from 12 MS patients (6 with AF) during mitral valve replacement surgery. From these tissues, miRNA expression profiles were created and analyzed using a human miRNA microarray. Results were validated via reverse-transcription and quantitative PCR for 5 selected miRNAs. Potential miRNA targets were predicted and their functions and potential pathways analyzed via the miRFocus database.ResultsThe expression levels of 22 miRNAs differed between the AF and NSR groups. Relative to NSR patients, in those with AF the expression levels of 45% (10/22) of these miRNAs were significantly higher, while those of the balance (55%, 12/22) were significantly lower. Potential miRNA targets and molecular pathways were identified.ConclusionsAF alters the miRNA expression profiles of the left atria of MS patients. These findings may be useful for the biological understanding of AF in MS patients.
Highlights
Structural changes of the left and right atria associated with atrial fibrillation (AF) in mitral stenosis (MS) patients are well known, and alterations in microRNA expression profiles of the right atria have been investigated
Clinical characteristics of the normal sinus rhythm (NSR) and AF patients There were no significant differences in terms of age, gender, or New York Heart Association (NYHA) functional classification between the NSR and AF groups
Preoperative color Doppler echocardiography showed that the size of the left atria of AF patients was significantly greater than that of NSR patients as previously reported [24], while there were no differences in the left ventricular end-diastolic diameter or ejection fraction between the two groups of patients (Table 1)
Summary
Structural changes of the left and right atria associated with atrial fibrillation (AF) in mitral stenosis (MS) patients are well known, and alterations in microRNA (miRNA) expression profiles of the right atria have been investigated. This study evaluated alterations in miRNA expression profiles of left atrial tissues from MS patients with AF relative to those with normal sinus rhythm (NSR). MicroRNAs (miRNAs) are regulators of gene expression at the post-transcriptional level [4], and appear to have regulatory roles that underlie the pathophysiology of AF. Many studies have shown that miRNAs regulate key genetic functions in cardiovascular biology and are crucial to the pathogenesis of cardiac diseases such as cardiac development [5], hypertrophy/ heart failure [6], remodeling [7], acute myocardial infarction [8], and myocardial ischemia-reperfusion injury [9]. There is a growing body of literature that indicates that many miRNAs are involved in AF through their target genes [7,10,11]
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