Circular <scp>RNAs</scp> in heart failure

Devaux, Yvan; Creemers, Esther E.; Boon, Reinier A.; Werfel, Stanislas; Thum, Thomas; Engelhardt, Stefan; Dimmeler, Stefanie; Squire, Iain B.

doi:10.1002/ejhf.801

Cited by 158 publications

(104 citation statements)

References 62 publications

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“…The comparison with previous studies on circRNAs and CAD is limited by the differences in the experimental designs and study populations. Nonetheless, these findings support the notion that circRNAs could be used for the assessment of cardiovascular disease 36 and coronary atherosclerotic disease. 15,37,38 This study provides a rationale for further investigations of circRNA quantification in the evaluation of suspected stable CAD.…”

Section: Discussionsupporting

confidence: 77%

Plasma circular RNA hsa_circ_0001445 and coronary artery disease: Performance as a biomarker

et al. 2020

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The role of circular RNAs (circRNAs) as biomarkers remains poorly characterized. Here, we investigated the performance of the circRNA hsa_circ_0001445 as a biomarker of coronary artery disease (CAD) in a real‐world clinical practice setting. Plasma hsa_circ_0001445 was measured in a study population of 200 consecutive patients with suspected stable CAD who had undergone coronary computed tomographic angiography (CTA). Multivariable logistic models were constructed combining conventional risk factors with established biomarkers and hsa_circ_0001445. Model robustness was internally validated by the bootstrap technique. Biomarker accuracy was evaluated using the C‐index. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were also calculated. Risk groups were developed via classification tree models. The stability of plasma hsa_circ_0001445 was evaluated under different clinical conditions. hsa_circ_0001445 levels were associated with higher coronary atherosclerosis extent and severity with a 2‐fold increase across tertiles (28.4%‐50.0%). Levels of hsa_circ_0001445 were proportional to coronary atherosclerotic burden, even after comprehensive adjustment for cardiovascular risk factors, medications, and established biomarkers (fully adjusted OR = 0.432 for hsa_circ_0001445 as a continuous variable and fully adjusted OR = 0.277 for hsa_circ_0001445 as a binary variable). The classification of patients was improved with the incorporation of hsa_circ_0001445 into a base clinical model (CM) composed of conventional cardiovascular risk factors, showing an IDI of 0.047 and NRI of 0.482 for hsa_circ_0001445 as a continuous variable and an IDI of 0.056 and NRI of 0.373 for hsa_circ_0001445 as a binary variable. A trend toward higher discrimination capacity was also observed (C‐indexCM = 0.833, C‐indexCM+continuous hsa_circ_0001445 = 0.856 and C‐indexCM+binary hsa_circ_0001445 = 0.855). Detailed analysis of stability showed that hsa_circ_0001445 was present in plasma in a remarkably stable form. In vitro, hsa_circ_0001445 was downregulated in extracellular vesicles secreted by human coronary smooth muscle cells upon exposure to atherogenic conditions. In patients with suspected stable CAD referred for coronary CTA, plasma hsa_circ_0001445 improves the identification of coronary artery atherosclerosis.

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Section: Discussionsupporting

confidence: 77%

Plasma circular RNA hsa_circ_0001445 and coronary artery disease: Performance as a biomarker

et al. 2020

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“…The potential of RNA methylation to be used as biomarker of cardiovascular disease is currently unknown. Considering the limitations to the use of the current gold‐standard biomarker of heart failure, N‐terminal pro‐B‐type natriuretic peptide, RNA methylation profiles may afford incremental diagnostic and prognostic value, as shown previously for circulating non‐coding RNAs . Sex differences shall be a central aspect of further adequately powered studies.…”

Section: Perspectivesmentioning

confidence: 95%

“…Considering the limitations to the use of the current gold-standard biomarker of heart failure, N-terminal pro-B-type natriuretic peptide, RNA methylation profiles may afford incremental diagnostic and prognostic value, as shown previously for circulating non-coding RNAs. 4,15,16 Sex differences shall be a central aspect of further adequately powered studies. Future studies may also look more into the regulation of m6A methylation and demethylation.…”

Section: Perspectivesmentioning

confidence: 99%

A role for m6A RNA methylation in heart failure development?

Devaux

Nossent

2019

European J of Heart Fail

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“…As previously stated, circRNAs possess strong biomarker potential and many studies aim to characterize new markers for risk stratification and early detection of diseases …”

Section: Circrna In Cardiovascular Diseasesmentioning

confidence: 99%

Circular RNAs: Methodological challenges and perspectives in cardiovascular diseases

Carrara

Fuschi

Ivan

et al. 2018

J Cellular Molecular Medi

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Circular RNAs are generated by back‐splicing of precursor‐mRNAs. Although they have been known for many years, only recently we have started to appreciate their widespread expression and their regulatory functions in a variety of biological processes. Not surprisingly, circular RNA dysregulation and participation in the pathogenic mechanisms have started to emerge in many instances, including cardiovascular diseases. Detection, differential expression analysis and validation are the three critical points for the characterization of any RNA, and circular RNAs are no exception. Their characteristics, however, generate several problems that are yet to be completely addressed, and literature still lacks comprehensive definitions of well‐defined best practices. We present a map of the current knowledge regarding circular RNAs and the critical issues limiting our understanding of their regulation and function. The goal was to provide the readers with the tools to critically decide which of the many approaches available is most suitable to their experimental plan. Although particularly focused on cardiovascular diseases, most critical issues concerning circular RNAs are common to many other fields of investigation.

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Circular RNAs in heart failure

Cited by 158 publications

References 62 publications

Plasma circular RNA hsa_circ_0001445 and coronary artery disease: Performance as a biomarker

Plasma circular RNA hsa_circ_0001445 and coronary artery disease: Performance as a biomarker

A role for m6A RNA methylation in heart failure development?

Circular RNAs: Methodological challenges and perspectives in cardiovascular diseases

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