Circulating microRNA expression profile and systemic right ventricular function in adults after atrial switch operation for complete transposition of the great arteries

Clare Tm Lai,Ava Kwong,Enders Ko Ng,Pak-Cheong Chow,Yiu-Fai Cheung

doi:10.1186/1471-2261-13-73

Abstract

BackgroundData on the use of circulating microRNAs (miRNAs) as biomarkers of cardiovascular diseases are emerging. Little, however, is known on the expression profile of circulating of microRNAs in congenital heart malformations with a systemic right ventricle that is prone to functional impairment. We aimed to test the hypothesis that circulating miRNA profile is altered in patients late after atrial switch operation for complete transposition of the great arteries (TGA) and further explored possible relationships between alteration of circulating miRNAs and systemic ventricular contractility.MethodsCirculating miRNA expression profiling of serum samples from 5 patients and 5 healthy controls was performed. The results were validated in 26 patients and 20 controls using real-time quantitative reverse-transcription polymerase chain reaction for candidate miRNAs with fold changes >3 by expression profiling. Systemic ventricular myocardial acceleration during isovolumic contraction (IVA) was determined by colour tissue Doppler echocardiography.ResultsCompared with controls, patients had significantly lower systemic ventricular IVA (p = 0.002). Of the 23 upregulated miRNAs identified by profiling, 11 were validated to be increased in patients compared with controls: miR-16, miR-106a, miR-144*, miR-18a, miR-25, miR-451, miR-486-3p, miR-486-5p, miR-505*, let-7e and miR-93. Among the validated 11 miRNAs, miR-18a (r = −0.45, p = 0.002) and miR-486-5p (r = −0.35, p = 0.018) correlated negatively with systemic ventricular IVA for the whole cohort.ConclusionsA distinct serum miRNA expression signature exists in adults with complete TGA after atrial switch operation, with serum miR-18a and miR-486-5p being associated with systemic ventricular contractility.

Highlights

Data on the use of circulating microRNAs as biomarkers of cardiovascular diseases are emerging
Further cardiac tissue-based studies have provided evidence of involvement of selective miRNAs in myocardial hypertrophy [11,12], regulation of cardiac apoptosis [13], regulation of cytoskeleton of cardiomyocytes and cardiac extracellular matrix [11], and neurohormonal activation [14,15], all of which contribute to adverse cardiac remodeling
Elevation of plasma cardiac-specific miRNA-208a has been shown to be potentially useful for early diagnosis of myocardial infarction [18], while plasma miR423-5p has been found to be increased in heart failure patients with reduced left ventricular (LV) ejection fraction [19]

Summary

Introduction

Data on the use of circulating microRNAs (miRNAs) as biomarkers of cardiovascular diseases are emerging. In determining the potential role of miRNAs in cardiovascular diseases, earlier studies have reported distinct profiles of differential tissue miRNA expression in human [8,9] and experimental models of heart failure [6,10]. Elevation of plasma cardiac-specific miRNA-208a has been shown to be potentially useful for early diagnosis of myocardial infarction [18], while plasma miR423-5p has been found to be increased in heart failure patients with reduced left ventricular (LV) ejection fraction [19]. A signature circulating miRNA expression profile has been reported in hypertensive patients [20] These encouraging data, albeit limited to date, provide evidence that circulating miRNAs may be potential biomarkers of cardiovascular diseases, in particular LV diseases

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