Serum circular RNAs act as blood-based biomarkers for hypertrophic obstructive cardiomyopathy
Sonnenschein, Kristina (Hannover Medical School. Department of Cardiology and Angiology)
Wilczek, Adriana Luisa (Institute of Molecular and Translational Therapeutic Strategies (IMTTS). Hannover Medical School)
Gonzalo Calvo, David de (Institut d'Investigació Biomèdica Sant Pau)
Pfanne, Angelika (Institute of Molecular and Translational Therapeutic Strategies (IMTTS). Hannover Medical School)
Derda, Anselm Arthur (Hannover Medical School. Department of Cardiology and Angiology)
Zwadlo, Carolin (Hannover Medical School. Department of Cardiology and Angiology)
Bavendiek, Udo (Hannover Medical School. Department of Cardiology and Angiology)
Bauersachs, Johann (Hannover Medical School. REBIRTH Center of Translational Regenerative Medicine)
Fiedler, Jan (Institute of Molecular and Translational Therapeutic Strategies (IMTTS). Hannover Medical School)
Thum, Thomas (Hannover Medical School. REBIRTH Center of Translational Regenerative Medicine)

Data:	2019
Resum:	Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and is associated with a high risk of sudden cardiac death. HCM is characterized by pronounced hypertrophy of cardiomyocytes, fiber disarray and development of fibrosis and can be divided into a non-obstructive (HNCM) and obstructive form (HOCM) therefore requiring personalized therapeutic therapies. In the present study, we investigated the expression patterns of several circulating circular RNAs (circRNAs) as potential biomarkers in patients with HCM. We included 64 patients with HCM and 53 healthy controls to the study and quantitatively measured the expression of a set of circRNAs already known to be associated with cardiac diseases (circDNAJC6) and/or being highly abundant in blood (circTMEM56 and circMBOAT2). Abundancy of circRNAs was then correlated to relevant clinical parameters. Serum expression levels of circRNAs DNAJC6, TMEM56 and MBOAT2 were downregulated in patients with HCM. The inverse association between circRNA levels and HCM remained unchanged even after adjusting for confounding factors. All circRNAs, evaluated separately or in combination, showed a robust discrimination capacity when comparing control subjects with HCM, HNCM or HOCM patients (AUC from 0. 722 to 0. 949). Two circRNAs, circTMEM56 and circDNAJC6, significantly negatively correlated with echocardiographic parameters for HOCM. Collectively, circulating circRNAs DNAJC6, TMEM56 and MBOAT2 can distinguish between healthy and HCM patients. In addition, circTMEM56 and circDNAJC6 could serve as indicators of disease severity in patients with HOCM. Thus, circRNAs emerge as novel biomarkers for HCM facilitating the clinical decision making in a personalized manner.
Ajuts:	Ministerio de Ciencia, Innovación y Universidades IJCI-2016-29393 Ministerio de Economía y Competitividad CB16/11/00403
Nota:	Altres ajuts: Junge Akademie (MHH); ERC grant Longheart; Deutsche Forschungsgemeinschaft (TRR_267, KFO311).
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Biomarkers ; Cardiomyopathy, Hypertrophic ; Case-Control Studies ; Cell-Free Nucleic Acids ; Echocardiography ; Female ; Heart Function Tests ; Humans ; Male ; Odds Ratio ; RNA, Circular ; ROC Curve
Publicat a:	Scientific reports, Vol. 9 Núm. 1 (january 2019) , p. 20350, ISSN 2045-2322

DOI: 10.1038/s41598-019-56617-2
PMID: 31889077

8 p, 1.1 MB

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