Circulating miR-423_5p fails as a biomarker for systemic ventricular function in adults after atrial repair for transposition of the great arteries
Introduction
MicroRNAs are endogenous, highly conserved, noncoding RNAs that regulate the stability and subsequent translation of nascent mRNA transcripts [1]. There are estimated to be more than 1000 different miRNAs, many of which are expressed in a tissue and cell-specific manner [2]. It was discovered only recently that miRNAs are also abundantly present in blood [2]. Aberrant expression profiles of miRNAs have been identified in blood of subjects with certain forms of cancer and myocardial injury [2], [3], [4], [5].
A recent study demonstrated a number of miRNAs as putative biomarkers for heart failure [2]. Tijsen and colleagues performed miRNA arrays on RNA isolated from patients with heart failure defined by the Framingham criteria and elevated NT-proBNP levels and compared these with healthy controls and patients with dyspnea attributable to other causes. One circulating miRNA in particular, miR-423_5p, was able to distinguish heart failure cases from the other cases with an area under the curve of 0.91 [2].
In patients after atrial repair for transposition of the great arteries (D-TGA), in whom the right ventricle supports the systemic circulation, dysfunction of the right ventricle is the most important contributor to morbidity and mortality [6]. Further progressive deterioration of systemic right ventricular function is common [6]. The role of microRNAs, in particular miR-423_5p, has not been evaluated in this patient group.
Section snippets
Participants
This study is part of an exercise intervention trial, which has been registered at www.clinicaltrials.gov (No. NCT00837603) [7].
Patients with previous atrial redirection procedure (Mustard) for D-TGA who met all the inclusion criteria were eligible for the study. The inclusion criteria were: stable NYHA class I/II, unchanged medication (angiotensin converting enzyme inhibitors, beta-blockers) for the last 6 months, no physical training program at present, and the physical and mental ability to
Results
Forty-one patients and 10 age- and sex-matched healthy controls were enrolled in this study. Table 1 shows the clinical characteristics of the study population. Cardiopulmonary exercise testing, echocardiography and MRI were only performed in the patients.
Discussion
In patients with a systemic right ventricle and reduced ejection fraction miR-423_5p levels are not elevated in comparison with healthy controls. Further, there is no difference of miR-423_5p levels in patients with a more severely reduced systemic ventricular function compared to patients with a moderately reduced or even normal ventricular function. This is contrast to findings recently reported in patients with left ventricular heart failure. Tijsen and colleagues showed recently that
Acknowledgment
This work was funded by grants of the German ministry for education and research (IFB-TX 0WO0802 to TT). The authors of this manuscript have certified that they comply with the principles of ethical publishing in the International Journal of Cardiology.
References (15)
- et al.
Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome
J Mol Cell Cardiol
(2011) - et al.
Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR)
Methods
(2010) - et al.
Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography
J Am Soc Echocardiogr
(2003) - et al.
Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography
J Am Soc Echocardiogr
(2002) - et al.
MicroRNAs and heart failure diagnosis: MiR-acle or MiR-age?
Circ Res
(2010) - et al.
MiR423-5p as a circulating biomarker for heart failure
Circ Res
(2010) - et al.
Circulating microRNAs: novel biomarkers for cardiovascular diseases?
Eur Heart J
(2010)
Cited by (47)
MicroRNAs in cardiovascular disease
2020, Hellenic Journal of CardiologyCitation Excerpt :More specifically, in this cohort study, patients with HF were found to have elevated circulating levels of miR-423-5p, and as a result they were successfully distinguished by healthy subjects.87 In total contrast to the role of miR-423-5p in left ventricular HF, Tutarel et al. reported no elevated levels of miR-423-5p in patients with right ventricular HF.88 Consequently, these findings imply the specificity of miR-423-5p augmentation only in left ventricular HF.
Sacubitril/valsartan for heart failure in adults with complex congenital heart disease
2020, International Journal of CardiologyCitation Excerpt :The remaining patients had a systemic right ventricle or a single ventricle physiology. Both have a quite different pathophysiology compared to the failure of a systemic left ventricle, [11] which could explain the different outcome in the current study. Not all of our patients reached the target dose for sacubitril/valsartan.
Modulating microRNAs in cardiac surgery patients: Novel therapeutic opportunities?
2017, Pharmacology and TherapeuticsCitation Excerpt :Thirdly, transposition of the great arteries (TGA) represents an important conotruncal anomaly involving challenging surgical repairs, whether the historical Senning/Mustard procedures (Love, Mehta, & Fuster, 2008) or more recently the arterial switch operation (Villafañe et al., 2014). One study targeted TGA patients (Tutarel et al., 2013) and specifically sought to investigate the possible role of miR-423-5p, as an HF biomarker, with the rationale of investigating a group of patients presenting with a systemic RV and reduced EF. While this study analysed a slightly larger number of samples (n = 41 TGA patients, n = 10 age/sex-matched controls), it was inconclusive, as levels of circulating miR-423-5p did not vary between patients and controls.
The Clinical Potential of Heart Failure-Related miRNAs
2017, Translating MicroRNAs to the ClinicMicroRNAs in heart failure: Non-coding regulators of metabolic function
2016, Biochimica et Biophysica Acta - Molecular Basis of DiseaseCitation Excerpt :However, conflicts in the alteration levels of circulating miRNA expression detected by different groups also occur. For example, in contrast to previous results showing miR-423-5p elevated in HF, Tutarel et al. failed to find changes of miR-423-5p levels in patients with right ventricular HF [42]. This discrepancy might be caused by differences in study population, in particular the importance of right versus LV failure, and the impact of right or LV overload versus ischemia in the study.