Plasma-derived exosomal let-7c-5p, miR-335-3p, and miR-652-3p as potential diagnostic biomarkers for stable coronary artery disease

Jian Han; Xiaogang Cui; Tianqi Yuan; Zhiming Yang; Yue Liu; Yajuan Ren; Changxin Wu; Yunfei Bian

doi:10.3389/fphys.2023.1161612

Plasma-derived exosomal let-7c-5p, miR-335-3p, and miR-652-3p as potential diagnostic biomarkers for stable coronary artery disease

Front Physiol. 2023 May 9:14:1161612. doi: 10.3389/fphys.2023.1161612. eCollection 2023.

Authors

Jian Han^{1

2}, Xiaogang Cui^{3

4}, Tianqi Yuan^{3

4}, Zhiming Yang², Yue Liu^{3

4}, Yajuan Ren², Changxin Wu^{3

4}, Yunfei Bian²

Affiliations

¹ Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China.
² Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
³ Key Lab of Medical Molecular Cell Biology of Shanxi Province, Institutes of Biomedical Sciences, Shanxi University, Taiyuan, China.
⁴ Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, China.

Abstract

Objectives: Circulating exosomal microRNAs (miRNAs) have been identified as promising biomarkers for diagnosis of cardiovascular diseases. Nevertheless, the diagnostic potential of miRNAs in circulating exosomes for stable coronary artery disease (SCAD) remains unclear. We aim here to analyze the exosomal differentially expressed miRNAs (DEmiRNAs) in plasma of SCAD patients and investigate their diagnostic potential as SCAD biomarkers. Methods: Plasma was collected from SCAD patients and healthy controls, and exosomes were isolated by ultracentrifugation. Exosomal DEmiRNAs were analyzed by small RNA sequencing and were further validated by quantitative real-time PCR (qRT-PCR) in a larger set of plasma samples. Relationships between plasma exosomal let-7c-5p, miR-335-3p, miR-652-3p, genders and Gensini Scores in patients with SCAD were analyzed using correlation analyses. Moreover, we conducted receiver operating characteristic (ROC) curves for these DEmiRNAs and analyzed their possible functions and signaling pathways. Results: Vesicles isolated from plasma displayed all characteristics of exosomes. In the small RNA sequencing study, a total of 12 DEmiRNAs were identified, among which seven were verified to be statistically significant by qRT-PCR. The areas under the ROC curves of exosomal let-7c-5p, miR-335-3p, and miR-652-3p were 0.8472, 0.8029, and 0.8009, respectively. Exosomal miR-335-3p levels were positively correlated with Gensini scores of patients with SCAD. Bioinformatics analysis revealed that these DEmiRNAs may be involved in the pathogenesis of SCAD. Conclusion: Our findings indicated that plasma exosomal let-7c-5p, miR-335-3p, and miR-652-3p can be used as promising biomarkers for diagnosis of SCAD. In addition, plasma exosomal miR-335-3p levels coordinated with severity of SCAD.

Keywords: biomarker; exosomes; microRNA; plasma; stable coronary artery disease.

Grants and funding

This research was funded by the National Natural Science Foundation of China (grant no. 8207022039), the Basic Research Project of Shanxi Science and Technology Department (grant no. 202203021222344) and Program of Graduate Innovation Research of Shanxi Province, China (grant no. 2021Y122).