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Shexiang Baoxin Pill Regulates Intimal Hyperplasia, Migration, and Apoptosis after Platelet-Derived Growth Factor-BB-Stimulation of Vascular Smooth Muscle Cells via miR-451

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Abstract

Objective

To investigate the regulatory roles of Shexiang Baoxin Pill (SXBXW) in neointimal formation and vascular smooth muscle cells (VSMCs) invasion and apoptosis as well as the potential molecular mechanisms using cultured VSMCs model of vascular injury (platelet-derived growth factor (PDGF)-BB-stimulated) in vitro.

Methods

VSMCs were randomly assigned to 5 groups: blank, PDGF-BB (20 ng/mL+ 0.1% DMSO), SXBXW-L (PDGF-BB 20 ng/mL + SXBXW low dose 0.625 g/L), SXBXW-M (PDGF-BB 20 ng/mL + SXBXW medium dose 1.25 g/L) and SXBXW-H (PDGF-BB 20 ng/mL+ SXBXW high dose 2.5 g/L) group. Cell proliferation was assessed using cell counting kit-8 (CCK-8) assay and bromodeoxyuridine (BrdU) incorporation assay, the migration effects were detected by Transwell assay, cell apoptosis rate was measured by the Annexin V/propidium iodide (PI) apoptosis kit. The markers of contractile phenotype of VSMCs were detected with immunofluorescent staining. To validate the effects of miR-451 in regulating proliferation, migration and apoptosis treated with SXBXW, miR-451 overexpression experiments were performed, the VSMCs were exposed to PDGF-BB 20 ng/mL + 0.1% DMSO and later divided into 4 groups: mimic-NC (multiplicity of infection, MOI=50), SXBXW (1.25 g/L) + mimic-NC, mimic-miR451 (MOI=50), and SXBXW (1.25 g/L) + mimic-miR451, and alterations of proteins related to the miR-451 pathway were analyzed using Western blot.

Results

PDGF-BB induced VSMCs injury causes acceleration of proliferation and migration. SXBXW inhibited phenotypic switching, proliferation and migration and promoted cell apoptosis in PDGF-BB-induced VSMCs. In addition, miR-451 was shown to be down-regulated in the VSMCs following PDGF-BB stimulation. SXBXW treatment enhanced the expression of miR-451 in PDGF-BB-induced VSMCs (P<0.05). Compared with SXBXW + mimic-NC and mimic-miR451 groups, the expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (Ywhaz) and p53 was further reduced in SXBXW + mimic-miR451 group, while activating transcription factor 2 (ATF2) was increased in VSMCs (P<0.05).

Conclusion

SXBXW regulated proliferation, migration and apoptosis via activation of miR-451 through ATF2, p53 and Ywhaz in PDGF-BB-stimulated VSMCs.

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Authors and Affiliations

  1. Department of Cardiology, Shuguang Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Yi-ping Li, Ting-ting Qiang, Ke-yan Wang & Xiao-long Wang

Authors
  1. Yi-ping Li
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  2. Ting-ting Qiang
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  3. Ke-yan Wang
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  4. Xiao-long Wang
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Contributions

Li YP and Wang XL conceptualized the ideas of this study. Li YP, Qiang TT and Wang KY performed all the experiments. Li YP wrote the original draft paper. Li YP, Qiang TT and Wang KY and Wang XL analyzed the experimental results and revised the paper. Li YP and Wang XL supervised the work and contributed to the study conceptualization. All authors have read and approved the final manuscript for submission.

Corresponding author

Correspondence to Xiao-long Wang.

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Conflict of Interest

The authors declare no conflict of interests in this work.

Supported by Shanghai Key Laboratory of Traditional Chinese Clinical Medicine (No. 14DZ2273200) and Shanghai Municipal Key Clinical Specialty (Department of TCM Cardiology, No. shslczdzk05301)

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Li, Yp., Qiang, Tt., Wang, Ky. et al. Shexiang Baoxin Pill Regulates Intimal Hyperplasia, Migration, and Apoptosis after Platelet-Derived Growth Factor-BB-Stimulation of Vascular Smooth Muscle Cells via miR-451. Chin. J. Integr. Med. 28, 785–793 (2022). https://doi.org/10.1007/s11655-022-2891-6

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  • DOI: https://doi.org/10.1007/s11655-022-2891-6

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