Improved medical care of congenital heart disease patients increased survival into adulthood from 15% in the 1960s to over 85% in the current era. As a consequence, the prevalence of adult congenital heart disease (ACHD) increased rapidly, 1 which is estimated to be .1 million ACHD patients in North America and 1.2 million in Europe. The growing number and aging of ACHD patients led to an overall increase in hospitalizations over the last decade and a substantial increase in patients presenting with heart failure (HF) ( 20%). 2 The incidence of first HF-admission was 1.2 per 1000 patientyears in the Dutch national 'CONCOR' registry. Patients admitted with HF had a five-fold higher risk of death than those not admitted. From the same registry, the mortality was 2.8% during a follow-up period of 24 865 patient-years. Chronic HF (26%) and sudden death (19%) were recorded most frequently. The median age at death from HF was 51.0 years (range: 20.3 -91.2 years). 3 In another ACHD cohort, sudden death (26%) was the most common cause of death, followed by progressive HF (21%) and perioperative death (18%). 4 Although patients with ACHD may not readily report symptoms, clinical HF is documented in 22.2% of patients with a Mustard
BackgroundMicroRNAs (miRNAs) are a class of regulatory RNAs that regulate gene expression post-transcriptionally. Little, however, is known on the expression profile of circulating miRNAs in Tetralogy of Fallot (TOF) patients late after surgical repair. In this study, we aimed to identify the specific patterns of circulating miRNAs in blood of patients with repaired, non-syndromic TOF and to assess whether these specific miRNAs may be useful to differentiate patients with and without heart failure.MethodsSurePrint™ 8 × 60 K Human v16 miRNA arrays were used to determine miRNA expression profiles in 15 healthy controls and 37 patients after TOF repair of whom 3 had symptomatic right heart failure. The expression levels of selected miRNAs have been validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Enrichment analyses of altered miRNA expression were predicted using bioinformatic tools.ResultsCompared with healthy controls, a total of 49, 58 and 77 miRNAs were found to be significantly altered in TOF patients (TOF-all), TOF patients with (TOF-HF) and without symptomatic right heart failure (TOF-noHF) (>2.0-fold change, adjusted P < 0.05), respectively. Three miRNAs namely miR-181d-5p, miR-206 and miR-625-5p were validated by RT-qPCR in all TOF groups. The area under the receiver operating characteristic curve (AUC) for miR-181d-5p, miR-206 and miR-625-5p were 0.987, 0.993 and 0.769 in TOF-all and 0.990, 0.994 and 0.749 in TOF-noHF, respectively. Moreover, expression levels of miR-625-5p, miR-1233-3p and miR-421 were lower in TOF-HF compared to TOF-noHF (P = 0.012).ConclusionsAltered expression levels of circulating miRNAs were found in TOF patients late after surgical repair and are different to those seen in the right ventricular myocardium of infants with TOF. Expression levels of miR-421, miR-1233-3p and miR-625-5p are lower in TOF patients with symptomatic right heart failure and thus may indicate disease progression in these patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1255-z) contains supplementary material, which is available to authorized users.
BackgroundMicroRNAs (miRNAs) are small RNAs regulating gene expression post-transcriptionally. While acquired changes of miRNA and mRNA profiles in cancer have been extensively studied, little is known about expression changes of circulating miRNAs and messenger RNAs (mRNA) in monogenic constitutional anomalies affecting several organ systems, like Marfan syndrome (MFS). We performed integrated miRNA and mRNA expression profiling in blood samples of Marfan patients in order to investigate deregulated miRNA and mRNA networks in these patients which could serve as potential diagnostic and prognostic tools for MFS therapy.MethodsMiRNA and mRNA expression profiles were determined in blood samples from MFS patients (n = 7) and from healthy volunteer controls (n = 7) by microarray analysis. Enrichment analyses of altered mRNA expression were identified using bioinformatic tools.ResultsA total of 28 miRNAs and 32 mRNAs were found to be significantly altered in MFS patients compared to controls (> 2.0-fold change, adjusted P < 0.05). The expression of 11 miRNA and 6 mRNA candidates was validated by RT-qPCR in an independent cohort of 26 MFS patients and 26 matched HV controls. Significant inverse correlations were evident between 8 miRNAs and 5 mRNAs involved in vascular pathology, inflammation and telomerase regulation. Significant positive correlations were present for 7 miRNAs with age, for 2 miRNAs with the MFS aortic root status (Z-score) and for 7 miRNAs with left ventricular end-diastolic diameter in MFS patients. In addition, miR-331-3p was significantly up-regulated in MFS patients without mitral valve prolapse (MVP) as compared with patients with MVP.ConclusionsOur data show deregulated gene and miRNA expression profiles in the peripheral blood of MFS patients, demonstrating several candidates for prognostic biomarkers for cardiovascular manifestations in MFS as well as targets for novel therapeutic approaches. A deregulation of miRNA expression seems to play an important role in MFS, highlighting the plethora of effects on post-transcriptional regulation of miRNAs and mRNAs initiated by constitutional mutations in single genes.Trial registration Nr: EA2/131/10. Registered 28 December, 2010Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1429-3) contains supplementary material, which is available to authorized users.
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