Cfa-circ002203 was upregulated in rapidly paced atria of dogs and involved in the mechanisms of atrial fibrosis

Wenfeng Shangguan; Tianshu Gu; Rukun Cheng; Xing Liu; Yu Liu; Shuai Miao; Weiding Wang; Fang Song; Hualing Wang; Tong Liu; Xue Liang

doi:10.3389/fcvm.2023.1110707

Cfa-circ002203 was upregulated in rapidly paced atria of dogs and involved in the mechanisms of atrial fibrosis

Front Cardiovasc Med. 2023 Aug 1:10:1110707. doi: 10.3389/fcvm.2023.1110707. eCollection 2023.

Authors

Wenfeng Shangguan^#¹, Tianshu Gu^#¹, Rukun Cheng^#¹, Xing Liu¹, Yu Liu², Shuai Miao¹, Weiding Wang¹, Fang Song³, Hualing Wang¹, Tong Liu¹, Xue Liang¹

Affiliations

¹ Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin, China.
² Department of Cardiology, Taikang Ningbo Hospital, Ningbo, China.
³ Department of Geriatric, The Second Hospital of Tianjin Medical University, Tianjin, China.

^# Contributed equally.

Abstract

Background and aims: The role of circular RNAs (circRNAs) in the pathophysiology of cardiovascular disease is gradually being elucidated; however, their roles in atrial fibrillation (AF)-related fibrosis are largely unknown. This study aimed to characterize the different circRNA profiles in the rapid-pacing atria of dogs and explore the mechanisms involved in atrial fibrosis.

Methods: A rapid right atrial-pacing model was established using electrical stimulation from a pacemaker. After 14 days, atrial tissue was collected for circRNA sequencing analysis. In vitro fibrosis was established by stimulating canine atrial fibroblasts with angiotensin II (Ang II). The fibroblasts were transfected with siRNA and overexpressing plasmids to explore the effects of cfa-circ002203 on fibroblast proliferation, migration, differentiation, and the expression of fibrosis-related proteins.

Results: In total, 146 differentially expressed circRNAs were screened, of which 106 were upregulated and 40 were downregulated. qRT-PCR analysis showed that cfa-circ002203 was upregulated in both in vivo and in vitro fibroblast fibrosis models. The upregulation of cfa-circ002203 enhanced proliferation and migration while weakening the apoptosis of fibroblasts. Western blotting showed that cfa-circ002203 overexpression increased the protein expression levels of fibrosis-related indicators (Col I, Col III, MMP2, MMP9, and α-SMA) and decreased the protein expression levels of pro-apoptotic factors (Bax and Caspase 3) in Ang II-induced fibroblast fibrosis.

Conclusion: Cfa-circ002203 might serve as an active promoter of the proliferation, migration, and fibrosis of atrial fibroblasts and is involved in AF-induced fibroblast fibrosis.

Keywords: atrial fibrillation; atrial fibrosis; bioinformatics; cfa-circ002203; high-throughput sequencing.

Grants and funding

This work was supported by the National Natural Science Foundation of China Youth Science Foundation Project [No. 81700304, No. 81900314 and No. 82000313]; Tianjin Health Research Project [No. TJWJ2023MS007]; The Scientific Research Fund Project of Key Laboratory of Second Hospital of Tianjin Medical University [No. 2019ZDSYS11, No. 2019ZDSYS10, No. 2019ZDSYS07]; The Research Fund for Central Laboratory of Second Hospital of Tianjin Medical University [No. 2020ydey05]; The Science and Technology Development Fund of Tianjin Education Commission for Higher Education [No. 2020KJ168] and Tianjin Key Medical Discipline (Specialty) Construction Project [TJYXZDXK-029A].