Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Dec 30;9(1):20350.
doi: 10.1038/s41598-019-56617-2.

Serum circular RNAs act as blood-based biomarkers for hypertrophic obstructive cardiomyopathy

Kristina Sonnenschein  1   2 , Adriana Luisa Wilczek  1 , David de Gonzalo-Calvo  1   3   4   5 , Angelika Pfanne  1 , Anselm Arthur Derda  1   2 , Carolin Zwadlo  2 , Udo Bavendiek  2 , Johann Bauersachs  2   6 , Jan Fiedler  1 , Thomas Thum  7   8   9
Affiliations

Serum circular RNAs act as blood-based biomarkers for hypertrophic obstructive cardiomyopathy

Kristina Sonnenschein et al. Sci Rep. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

T.T. has filed patents in the field of non-coding RNAs and is founder and holds shares of Cardior Pharmaceuticals GmbH. D.d.G.C. have licensed a patent on microRNAs as biomarkers. Other authors have no conflicts of interest.

Figures

Figure 1
Figure 1
Expression levels of circular RNAs were measured in serum of patients in the study groups: (A) circDNAJC6; (B) circMBOAT2; (C) circTEM56. Differences between groups were analyzed using Kruskal–Wallis test and/or Mann–Whitney U test. Data represent the medians (IQR), minimum and maximum. P‐values describe the significance level of differences for each comparison. HCM: hypertrophic cardiomyopathy; HNCM: non-obstructive hypertrophic cardiomyopathy; HOCM: obstructive hypertrophic cardiomyopathy.
Figure 2
Figure 2
ROC curve analyses of circulating circular RNAs. (A) circDNAJC6; (B) circMBOAT2; (C) circTMEM56. Data are presented as the area under the ROC curve (AUC) and 95% confidence intervals (CI). HCM: hypertrophic cardiomyopathy; HNCM: non-obstructive hypertrophic cardiomyopathy; HOCM: obstructive hypertrophic cardiomyopathy.
Figure 3
Figure 3
Correlations between circulating circular RNAs and echocardiographic parameters in patients with obstructive hypertrophic cardiomyopathy (HOCM). (A) circDNAJC6 vs LVOT gr. Max.; (B) circTEME56 vs IVS. Correlations between variables were analyzed using Spearman’s rho coefficient. LVOT gr. Max.: maximum gradient in left ventricular outflow tract. IVS: interventricular septum.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Maron BJ. Clinical Course and Management of Hypertrophic Cardiomyopathy. N Engl J Med. 2018;379:655–668. doi: 10.1056/NEJMra1710575. - DOI - PubMed
    1. Maron BJ, Rowin EJ, Maron MS. Global Burden of Hypertrophic Cardiomyopathy. JACC Heart Fail. 2018;6:376–378. doi: 10.1016/j.jchf.2018.03.004. - DOI - PubMed
    1. Semsarian C, Ingles J, Maron MS, Maron BJ. New perspectives on the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2015;65:1249–1254. doi: 10.1016/j.jacc.2015.01.019. - DOI - PubMed
    1. Authors/Task Force members. Elliott PM, et al. ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC) Eur Heart J. 2014;2014(35):2733–2779. - PubMed
    1. de Gonzalo-Calvo D, et al. Circulating non-coding RNAs in biomarker-guided cardiovascular therapy: a novel tool for personalized medicine? Eur Heart J. 2019;40:1643–1650. doi: 10.1093/eurheartj/ehy234. - DOI - PMC - PubMed

Publication types