Long Noncoding RNA UCA1 Correlates With Electropathology in Patients With Atrial Fibrillation

Kennedy S. Ramos; Jin Li; Leonoor F.J. Wijdeveld; Mathijs S. van Schie; Yannick J.H.J. Taverne; Reinier A. Boon; Natasja M.S. de Groot; Bianca J.J.M. Brundel

doi:10.1016/j.jacep.2023.02.018

Long Noncoding RNA UCA1 Correlates With Electropathology in Patients With Atrial Fibrillation

Kennedy S. Ramos, Jin Li, Leonoor F.J. Wijdeveld, Mathijs S. van Schie, Yannick J.H.J. Taverne, Reinier A. Boon, Natasja M.S. de Groot, Bianca J.J.M. Brundel^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

6 Citations (Scopus)

Abstract

Background: Perpetuation of atrial fibrillation (AF) is rooted in derailment of molecular proteostasis pathways that cause electrical conduction disorders that drive AF. Emerging evidence indicates a role for long noncoding RNAs (lncRNAs) in the pathophysiology of cardiac diseases, including AF. Objectives: In the present study, the authors explored the association between 3 cardiac lncRNAs and the degree of electropathology. Methods: Patients had paroxysmal AF (ParAF) (n = 59), persistent AF (PerAF) (n = 56), or normal sinus rhythm without a history of AF (SR) (n = 70). The relative expression levels of urothelial carcinoma–associated 1 (UCA1), OXCT1-AS1 (SARRAH), and the mitochondrial lncRNA uc022bqs.q (LIPCAR) were measured by means of quantitative reverse-transcription polymerase chain reaction in the right atrial appendage (RAA) or serum (or both). A selection of the patients was subjected to high-resolution epicardial mapping to evaluate electrophysiologic features during SR. Results: The expression levels of SARRAH and LIPCAR were decreased in RAAs of all AF patients compared with SR. Also, in RAAs, UCA1 levels significantly correlated with the percentage of conduction block and delay, and inversely with conduction velocity, indicating that UCA1 levels in RAA reflect the degree of electrophysiologic disorders. Moreover, in serum samples, SARRAH and UCA1 levels were increased in the total AF group and ParAF patients compared with SR. Conclusions: LncRNAs SARRAH and LIPCAR are reduced in RAA of AF patients, and UCA1 levels correlate with electrophysiologic conduction abnormalities. Thus, RAA UCA1 levels may aid staging of electropathology severity and act as a patient-tailored bioelectrical fingerprint.

Original language	English
Pages (from-to)	1097-1107
Number of pages	11
Journal	JACC: Clinical Electrophysiology
Volume	9
Issue number	7
DOIs	https://doi.org/10.1016/j.jacep.2023.02.018
Publication status	Published - Jul 2023

Bibliographical note

Funding Information:
The authors kindly thank all patients who participated in this study, as well as the cardiothoracic surgeons from Erasmus Medical Center: E. Boersma, MD, A.J.Q.M. Muskens, RN, P. Knops, MSc, and J. Claesen, PhD.

FUNDING SUPPORT AND AUTHOR DISCLOSURES:
This research was funded by the Atrial-Fibrillation-InnovationPlatform (AFIPonline.org), Dutch Heart Foundation (2020-
2020B003, DnAFix), NWO (NWA.1389.20.157 CIRCULAR), CVONSTW2016-14728 AFFIP, NWO-Vidi (2016-91717339 to Dr de Groot),
and Medical Delta. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2023 American College of Cardiology Foundation

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@article{c70a41ad0db5478489f55e55bc0f5210,

title = "Long Noncoding RNA UCA1 Correlates With Electropathology in Patients With Atrial Fibrillation",

abstract = "Background: Perpetuation of atrial fibrillation (AF) is rooted in derailment of molecular proteostasis pathways that cause electrical conduction disorders that drive AF. Emerging evidence indicates a role for long noncoding RNAs (lncRNAs) in the pathophysiology of cardiac diseases, including AF. Objectives: In the present study, the authors explored the association between 3 cardiac lncRNAs and the degree of electropathology. Methods: Patients had paroxysmal AF (ParAF) (n = 59), persistent AF (PerAF) (n = 56), or normal sinus rhythm without a history of AF (SR) (n = 70). The relative expression levels of urothelial carcinoma–associated 1 (UCA1), OXCT1-AS1 (SARRAH), and the mitochondrial lncRNA uc022bqs.q (LIPCAR) were measured by means of quantitative reverse-transcription polymerase chain reaction in the right atrial appendage (RAA) or serum (or both). A selection of the patients was subjected to high-resolution epicardial mapping to evaluate electrophysiologic features during SR. Results: The expression levels of SARRAH and LIPCAR were decreased in RAAs of all AF patients compared with SR. Also, in RAAs, UCA1 levels significantly correlated with the percentage of conduction block and delay, and inversely with conduction velocity, indicating that UCA1 levels in RAA reflect the degree of electrophysiologic disorders. Moreover, in serum samples, SARRAH and UCA1 levels were increased in the total AF group and ParAF patients compared with SR. Conclusions: LncRNAs SARRAH and LIPCAR are reduced in RAA of AF patients, and UCA1 levels correlate with electrophysiologic conduction abnormalities. Thus, RAA UCA1 levels may aid staging of electropathology severity and act as a patient-tailored bioelectrical fingerprint.",

author = "Ramos, {Kennedy S.} and Jin Li and Wijdeveld, {Leonoor F.J.} and {van Schie}, {Mathijs S.} and Taverne, {Yannick J.H.J.} and Boon, {Reinier A.} and {de Groot}, {Natasja M.S.} and Brundel, {Bianca J.J.M.}",

note = "Funding Information: The authors kindly thank all patients who participated in this study, as well as the cardiothoracic surgeons from Erasmus Medical Center: E. Boersma, MD, A.J.Q.M. Muskens, RN, P. Knops, MSc, and J. Claesen, PhD. FUNDING SUPPORT AND AUTHOR DISCLOSURES: This research was funded by the Atrial-Fibrillation-InnovationPlatform (AFIPonline.org), Dutch Heart Foundation (2020- 2020B003, DnAFix), NWO (NWA.1389.20.157 CIRCULAR), CVONSTW2016-14728 AFFIP, NWO-Vidi (2016-91717339 to Dr de Groot), and Medical Delta. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2023 American College of Cardiology Foundation",

year = "2023",

month = jul,

doi = "10.1016/j.jacep.2023.02.018",

language = "English",

volume = "9",

pages = "1097--1107",

journal = "JACC: Clinical Electrophysiology",

issn = "2405-500X",

publisher = "Elsevier Inc.",

number = "7",

}

TY - JOUR

T1 - Long Noncoding RNA UCA1 Correlates With Electropathology in Patients With Atrial Fibrillation

AU - Ramos, Kennedy S.

AU - Li, Jin

AU - Wijdeveld, Leonoor F.J.

AU - van Schie, Mathijs S.

AU - Taverne, Yannick J.H.J.

AU - Boon, Reinier A.

AU - de Groot, Natasja M.S.

AU - Brundel, Bianca J.J.M.

N1 - Funding Information: The authors kindly thank all patients who participated in this study, as well as the cardiothoracic surgeons from Erasmus Medical Center: E. Boersma, MD, A.J.Q.M. Muskens, RN, P. Knops, MSc, and J. Claesen, PhD. FUNDING SUPPORT AND AUTHOR DISCLOSURES: This research was funded by the Atrial-Fibrillation-InnovationPlatform (AFIPonline.org), Dutch Heart Foundation (2020- 2020B003, DnAFix), NWO (NWA.1389.20.157 CIRCULAR), CVONSTW2016-14728 AFFIP, NWO-Vidi (2016-91717339 to Dr de Groot), and Medical Delta. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: © 2023 American College of Cardiology Foundation

PY - 2023/7

Y1 - 2023/7

N2 - Background: Perpetuation of atrial fibrillation (AF) is rooted in derailment of molecular proteostasis pathways that cause electrical conduction disorders that drive AF. Emerging evidence indicates a role for long noncoding RNAs (lncRNAs) in the pathophysiology of cardiac diseases, including AF. Objectives: In the present study, the authors explored the association between 3 cardiac lncRNAs and the degree of electropathology. Methods: Patients had paroxysmal AF (ParAF) (n = 59), persistent AF (PerAF) (n = 56), or normal sinus rhythm without a history of AF (SR) (n = 70). The relative expression levels of urothelial carcinoma–associated 1 (UCA1), OXCT1-AS1 (SARRAH), and the mitochondrial lncRNA uc022bqs.q (LIPCAR) were measured by means of quantitative reverse-transcription polymerase chain reaction in the right atrial appendage (RAA) or serum (or both). A selection of the patients was subjected to high-resolution epicardial mapping to evaluate electrophysiologic features during SR. Results: The expression levels of SARRAH and LIPCAR were decreased in RAAs of all AF patients compared with SR. Also, in RAAs, UCA1 levels significantly correlated with the percentage of conduction block and delay, and inversely with conduction velocity, indicating that UCA1 levels in RAA reflect the degree of electrophysiologic disorders. Moreover, in serum samples, SARRAH and UCA1 levels were increased in the total AF group and ParAF patients compared with SR. Conclusions: LncRNAs SARRAH and LIPCAR are reduced in RAA of AF patients, and UCA1 levels correlate with electrophysiologic conduction abnormalities. Thus, RAA UCA1 levels may aid staging of electropathology severity and act as a patient-tailored bioelectrical fingerprint.

AB - Background: Perpetuation of atrial fibrillation (AF) is rooted in derailment of molecular proteostasis pathways that cause electrical conduction disorders that drive AF. Emerging evidence indicates a role for long noncoding RNAs (lncRNAs) in the pathophysiology of cardiac diseases, including AF. Objectives: In the present study, the authors explored the association between 3 cardiac lncRNAs and the degree of electropathology. Methods: Patients had paroxysmal AF (ParAF) (n = 59), persistent AF (PerAF) (n = 56), or normal sinus rhythm without a history of AF (SR) (n = 70). The relative expression levels of urothelial carcinoma–associated 1 (UCA1), OXCT1-AS1 (SARRAH), and the mitochondrial lncRNA uc022bqs.q (LIPCAR) were measured by means of quantitative reverse-transcription polymerase chain reaction in the right atrial appendage (RAA) or serum (or both). A selection of the patients was subjected to high-resolution epicardial mapping to evaluate electrophysiologic features during SR. Results: The expression levels of SARRAH and LIPCAR were decreased in RAAs of all AF patients compared with SR. Also, in RAAs, UCA1 levels significantly correlated with the percentage of conduction block and delay, and inversely with conduction velocity, indicating that UCA1 levels in RAA reflect the degree of electrophysiologic disorders. Moreover, in serum samples, SARRAH and UCA1 levels were increased in the total AF group and ParAF patients compared with SR. Conclusions: LncRNAs SARRAH and LIPCAR are reduced in RAA of AF patients, and UCA1 levels correlate with electrophysiologic conduction abnormalities. Thus, RAA UCA1 levels may aid staging of electropathology severity and act as a patient-tailored bioelectrical fingerprint.

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JO - JACC: Clinical Electrophysiology

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ER -

Long Noncoding RNA UCA1 Correlates With Electropathology in Patients With Atrial Fibrillation

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