Thromb Haemost 2023; 123(01): 097-107
DOI: 10.1055/s-0042-1757875
Atherosclerosis and Ischaemic Disease

CircRNA circCOL1A1 Acts as a Sponge of miR-30a-5p to Promote Vascular Smooth Cell Phenotype Switch through Regulation of Smad1 Expression

Meng Ye*,#
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
,
Qihong Ni*,#
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
,
Han Wang*,#
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
,
Yuli Wang
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
,
Yongjie Yao
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
,
Yinan Li
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
,
Weilun Wang
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
,
Shuofei Yang
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
,
Jiaquan Chen
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
,
Lei Lv
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
,
Yiping Zhao
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
,
Guanhua Xue
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
,
Xiangjiang Guo*,#
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
,
Lan Zhang*,#
1   Department of Vascular Surgery, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
› Author Affiliations
Funding This work was supported by the National Nature Science Foundation of China (81670442 to Zhang L., 81800415 to Li Y., and 82000447 to Ni Q.) and “Star of Jiao-Tong University” Medical-Industry Interdisciplinary Research Fund (02.101004.282.022 to Zhang L.)


Abstract

Phenotypic switch of vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of atherosclerosis. The mRNA expression of the synthetic biomarker Collagen Type I Alpha 1 Chain (COL1A1) gene is upregulated during the switch of VSMCs from the contractile to the synthetic phenotype. The association of noncoding circular RNAs transcribed by the COL1A1 gene with VSMC phenotype alteration and atherogenesis remains unclear. Here we reported a COL1A1 circular RNA (circCOL1A1) which is specifically expressed in VSMCs and is upregulated during phenotype alteration of VSMCs. CircCOL1A1 is also detectable in the serum or plasma. Healthy vascular tissues have a low expression of CircCOL1A1, while it is upregulated in atherosclerosis patients. Through ex vivo and in vitro assays, we found that circCOL1A1 can promote VSMC phenotype switch. Mechanistic analysis showed that circCOL1A1 may exert its function as a competing endogenous RNA of miR-30a-5p. Upregulation of circCOL1A1 ameliorates the inhibitory effect of miR-30a-5p on its target SMAD1, which leads to suppression of transforming growth factor-β (TGF-β) signaling. Our findings demonstrate that circCOL1A1 promotes the phenotype switch of VSMCs through the miR-30a-5p/SMAD1/TGF-β axis and it may serve as a novel marker of atherogenesis or as a therapeutic target for atherosclerosis.

Ethics Approval and Consent to Participate

All procedures were approved by the Research Ethics Committee of the Renji Hospital (RA-2020–071). All patients included in this research provided written informed consent.


Availability of Data

The data that support the findings of this study are available from the corresponding author upon reasonable request.


Author Contribution

Concept and design: L.Z. and X.G. Acquisition of data: M.Y., Q.N., and H.W. Data analysis and interpretation: M.Y., X.G., and H.W. Drafting the manuscript: M.Y. and X.G. Critical revision of the manuscript: Y.Z, G.X., and X.G. Statistical analysis: Y.L., M.Y., X.G., and G.X. Acquisition of funding: Y.L., L.Z., and Q.N. Administrative, technical, and/or material support: Y.W., Y.Y., W.W., S.Y., J.C., L.L., Y.Z., and G.X.


*,# These authors contributed equally to this study.


Supplementary Material



Publication History

Received: 22 September 2021

Accepted: 27 August 2022

Article published online:
03 December 2022

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