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Original Article

Korean J Physiol Pharmacol 2022; 26(6): 519-530

Published online November 1, 2022

Copyright © Korean J Physiol Pharmacol.

Lactate promotes vascular smooth muscle cell switch to a synthetic phenotype by inhibiting miR-23b expression

Yanchao Hu, Chunyan Zhang, Yajie Fan, Yan Zhang, Yiwen Wang, and Congxia Wang*

Department of Cardiovascular Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi 710004, China

Correspondence to:Congxia Wang

Author contributions: Y.H., C.Z., and C.W. designed the experiments. Y.H. wrote the manuscript. C.Z. and Y.F. performed the experiments. Y.Z. and Y.W. analyzed the data. C.W. revised the manuscript. All the authors have read and approved the final version of the manuscript.

Received: July 18, 2022; Revised: September 2, 2022; Accepted: September 13, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Recent research indicates that lactate promotes the switching of vascular smooth muscle cells (VSMCs) to a synthetic phenotype, which has been implicated in various vascular diseases. This study aimed to investigate the effects of lactate on the VSMC phenotype switch and the underlying mechanism. The CCK-8 method was used to assess cell viability. The microRNAs and mRNAs levels were evaluated using quantitative PCR. Targets of microRNA were predicted using online tools and confirmed using a luciferase reporter assay. We found that lactate promoted the switch of VSMCs to a synthetic phenotype, as evidenced by an increase in VSMC proliferation, mitochondrial activity, migration, and synthesis but a decrease in VSMC apoptosis. Lactate inhibited miR-23b expression in VSMCs, and miR-23b inhibited VSMC's switch to the synthetic phenotype. Lactate modulated the VSMC phenotype through downregulation of miR-23b expression, suggesting that overexpression of miR-23b using a miR-23b mimic attenuated the effects of lactate on VSMC phenotype modulation. Moreover, we discovered that SMAD family member 3 (SMAD3) was the target of miR-23b in regulating VSMC phenotype. Further findings suggested that lactate promotes VSMC switch to synthetic phenotype by targeting SMAD3 and downregulating miR-23b. These findings suggest that correcting the dysregulation of miR-23b/SMAD3 or lactate metabolism is a potential treatment for vascular diseases.

Keywords: Lactate, miR-23b, Phenotype switch, SMAD3, Smooth muscle