Plasma MicroRNAs as noninvasive diagnostic biomarkers in patients with Brugada syndrome

Ikeuchi, Yoshihiro; Ochi, Hidenori; Motoda, Chikaaki; Tokuyama, Takehito; Okubo, Yousaku; Okamura, Sho; Miyauchi, Syunsuke; Miyamoto, Shoko; Uotani, Yukimi; Onohara, Yuko; Nakashima, Mika; Akiyama, Rie; Tahara, Hidetoshi; Chayama, Kazuaki; Kihara, Yasuki; Nakano, Yukiko

doi:10.1371/journal.pone.0261390

Cited by 2 publications

(2 citation statements)

References 35 publications

(39 reference statements)

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“…No comparison between symptomatic and asymptomatic individuals was performed. 34 Thus, so far, our study is the only one suggesting a distinct miRNA expression profile in Brugada patients with ventricular arrhythmia. The distinct miRNA signature compared with our study could be explained by differences in the source of the miRNAs, the study population and the biostatistical methods used.…”

Section: Discussionmentioning

confidence: 69%

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Leucocyte-derived micro-RNAs as candidate biomarkers in Brugada syndrome

et al. 2023

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Aims Risk stratification for sudden cardiac death in patients with Brugada syndrome remains a major challenge. Contemporary risk prediction models have only modest predictive value. The aim of this study was to assess the role of micro-RNAs from peripheral blood as candidate biomarkers in Brugada syndrome. Methods and results In this prospective study, Brugada patients and unaffected control individuals were enrolled for analysis of leucocyte-derived microRNAs (miRNAs) levels. Expression levels of 798 different circulating miRNAs were analysed on the NanoString® nCounter platform. All results were cross-validated by using a quantitative polymerase chain reaction. Micro-RNA expression levels of Brugada patients were compared with clinical data. A total of 21 definite Brugada patients (38% with a history of ventricular arrhythmia or cardiac arrest) and 30 unaffected control individuals were included in the study. Micro-RNA analysis showed a distinct expression profile in Brugada patients with 42 differentially expressed markers (38 up-regulated, 4 down-regulated miRNAs). The symptom status of Brugada patients was associated with a distinct miRNA signature. Micro-RNAs 145-5p and 585-3p were significantly up-regulated in symptomatic Brugada patients (P = 0.04). Incorporating miRNAs 145-5p and 585-3p into a multivariable model demonstrated significantly increased symptom prediction (area under the curve = 0.96; 95% confidence interval: 0.88–1.00). Conclusion Brugada patients display a distinct miRNA expression profile compared with unaffected control individuals. There is also evidence that certain miRNAs (miR-145-5p and miR-585-3p) are associated with the symptom status of Brugada patients. The results suggest the principal utility of leucocyte-derived miRNAs as prognostic biomarkers for Brugada syndrome.

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Section: Discussionmentioning

confidence: 69%

“…A second study by Ikeuchi et al . 34 performed miRNA analysis in plasma samples and screened 2555 miRNAs using microarrays in a cohort of Japanese Brugada patients and unaffected controls. They also found a distinct miRNA signature in Brugada patients but reported different target miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Leucocyte-derived micro-RNAs as candidate biomarkers in Brugada syndrome

et al. 2023

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Noncoding RNAs and Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Cardiac Arrhythmic Brugada Syndrome

Theisen,

Holtz,

Rajagopalan

2023

Cells

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Hundreds of thousands of people die each year as a result of sudden cardiac death, and many are due to heart rhythm disorders. One of the major causes of these arrhythmic events is Brugada syndrome, a cardiac channelopathy that results in abnormal cardiac conduction, severe life-threatening arrhythmias, and, on many occasions, death. This disorder has been associated with mutations and dysfunction of about two dozen genes; however, the majority of the patients do not have a definite cause for the diagnosis of Brugada Syndrome. The protein-coding genes represent only a very small fraction of the mammalian genome, and the majority of the noncoding regions of the genome are actively transcribed. Studies have shown that most of the loci associated with electrophysiological traits are located in noncoding regulatory regions and are expected to affect gene expression dosage and cardiac ion channel function. Noncoding RNAs serve an expanding number of regulatory and other functional roles within the cells, including but not limited to transcriptional, post-transcriptional, and epigenetic regulation. The major noncoding RNAs found in Brugada Syndrome include microRNAs; however, others such as long noncoding RNAs are also identified. They contribute to pathogenesis by interacting with ion channels and/or are detectable as clinical biomarkers. Stem cells have received significant attention in the recent past, and can be differentiated into many different cell types including those in the heart. In addition to contractile and relaxational properties, BrS-relevant electrophysiological phenotypes are also demonstrated in cardiomyocytes differentiated from stem cells induced from adult human cells. In this review, we discuss the current understanding of noncoding regions of the genome and their RNA biology in Brugada Syndrome. We also delve into the role of stem cells, especially human induced pluripotent stem cell-derived cardiac differentiated cells, in the investigation of Brugada syndrome in preclinical and clinical studies.

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Plasma MicroRNAs as noninvasive diagnostic biomarkers in patients with Brugada syndrome

Cited by 2 publications

References 35 publications

Leucocyte-derived micro-RNAs as candidate biomarkers in Brugada syndrome

Leucocyte-derived micro-RNAs as candidate biomarkers in Brugada syndrome

Noncoding RNAs and Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Cardiac Arrhythmic Brugada Syndrome

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