Log in

Effect of High Magnesium and Astragaloside IV on Vascular Endothelial Cells

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Percutaneous coronary intervention (PCI) is the main treatment for patients with severe coronary vascular stenosis. However, In-stent neo-atherosclerosis (ISNA) is an important clinical complication in patients after PCI, which is mainly caused by a persistent inflammatory response and endothelial insufficiency. In the cardiovascular field, magnesium-based scaffolds stand out due to their properties. Magnesium plays a key role in regulating cardiovascular physiology. Magnesium deficiency can promote endothelial cell dysfunction, which contributes to the formation of atherosclerosis. Since astragaloside IV (AS‑IV) has been proven to have potent cardioprotective effects, we asked whether high levels of magnesium cooperate with AS‑IV might have effects on endothelial function and ISNA. We performed in vitro experiments on endothelial cells. Being treated with different concentrations of magnesium or/and AS-IV, the cell growth and migration were detected by CCK-8 and wound healing assay, respectively. The pro-inflammatory factors tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), adhesion molecule vascular cell adhesion molecule-1 (VCAM-1), and NF-kB were determined by qRT-PCR, ELISA kits or western blot. Results showed that high magnesium and AS-IV improved endothelial function, including promoting cell migration and decreasing the content of TNF-α, IL-6, VCAM-1, and NF-kB. With the supplement of AS-IV, additive magnesium maintains cell proliferation, migration, and function of endothelial cells. In conclusion, these findings suggest that high magnesium and AS‑IV could improve vascular endothelial dysfunction. Early detection and treatment for neo-atherosclerosis may be of great clinical significance for improving stent implantation efficacy and long-term prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

AS‑IV:

Astragaloside IV

CHD:

Coronary heart disease

CVD:

Cardiovascular disease

IL-6:

Interleukin 6

ISNA:

In-stent neo-atherosclerosis

ISR:

In-stent restenosis

LST:

Late stent thrombosis

PCI:

Percutaneous coronary intervention

TNF-α:

Tumor necrosis factor α

VCAM-1:

Vascular cell adhesion molecule-1

References

  1. Fedele, G., Castiglioni, S., & Maier, J. A., et al. (2021). High magnesium and sirolimus on rabbit vascular cells-An in vitro proof of concept. Materials, 14, 1970.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Nusca, A., Viscusi, M. M., & Piccirillo, F., et al. (2022). In stent neo-atherosclerosis: Pathophysiology, clinical implications, prevention, and therapeutic approaches. Life, 12, 393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Tan, Y. Q., Chen, H. W., & Li, J. (2020). Astragaloside IV: An effective drug for the treatment of cardiovascular diseases. Drug Design, Development and Therapy, 14, 3731–3746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Liu, C., Chen, L., & Zhang, K., et al. (2022). Tailoring ZE21B alloy with nature-inspired extracellular matrix secreted by micro-patterned smooth muscle cells and endothelial cells to promote surface biocompatibility. International Journal of Molecular Sciences, 23, 3180.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hou, Z., **ang, M., & Chen, N., et al. (2021). The biological responses and mechanisms of endothelial cells to magnesium alloy. Regenerative Biomaterials, 8, rbab017.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Almousa, L. A., Salter, A. M., & Castellanos, M., et al. (2022). The response of the human umbilical vein endothelial cell transcriptome to variation in magnesium concentration. Nutrients, 14, 3586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Meng, P., Yang, R., & Jiang, F., et al. (2021). Molecular mechanism of astragaloside IV in improving endothelial dysfunction of cardiovascular diseases mediated by oxidative stress. Oxidative Medicine and Cellular Longevity, 2021, 8.

    Article  Google Scholar 

  8. Yang, C., Pan, Q., & Ji, K., et al. (2023). Review on the protective mechanism of astragaloside IV against cardiovascular diseases. Frontiers in Pharmacology, 14, 1187910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Simion, V., Zhou, H., & Pierce, J. B., et al. (2020). LncRNA VINAS regulates atherosclerosis by modulating NF-kappaB and MAPK signaling. JCI Insight, 5(21), 1–15.

    Article  Google Scholar 

  10. Park, S. J., Kang, S. J., & Virmani, R., et al. (2012). In-stent neoatherosclerosis: A final common pathway of late stent failure. Journal of the American College of Cardiology, 59, 2051–2057.

    Article  PubMed  Google Scholar 

  11. Liu, M., & Dudley, S. C. (2020). Magnesium, oxidative stress, inflammation, and cardiovascular disease. Antioxidants, 9, 32.

    Article  Google Scholar 

  12. Qi, H., Heise, S., & Zhou, J., et al. (2019). Electrophoretic deposition of bioadaptive drug delivery coatings on magnesium alloy for bone repair. ACS Applied Materials and Interfaces, 11, 8625–8634.

    Article  CAS  PubMed  Google Scholar 

  13. Maier, J. A., Castiglioni, S., & Locatelli, L., et al. (2021). Magnesium and inflammation: Advances and perspectives. Seminars in Cell and Developmental Biology, 115, 37–44.

    Article  CAS  PubMed  Google Scholar 

  14. Echeverry-Rendon, M., Echeverria, F., & Buikema, H., et al. (2022). Endothelial function after the exposition of magnesium degradation products. Biomaterials Advances, 134, 112693.

    Article  CAS  PubMed  Google Scholar 

  15. Ye, L., Zhang, C., & Duan, Q., et al. (2023). Association of magnesium depletion score with cardiovascular disease and its association with longitudinal mortality in patients with cardiovascular disease. Journal of the American Heart Association, 12(e030077), 1–11.

    Google Scholar 

  16. Murphy, C., Byrne, J., & Keogh, J. B., et al. (2021). The acute effect of magnesium supplementation on endothelial function: A randomized cross-over pilot study. International Journal of Environmental Research and Public Health, 18, 5303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Locatelli, L., Fedele, G., & Castiglioni, S., et al. (2021). Magnesium deficiency induces lipid accumulation in vascular endothelial cells via oxidative stress-The potential contribution of EDF-1 and PPARgamma. International Journal of Molecular Sciences, 22, 1050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Xu, Z., Zhou, H., & Zhang, Y., et al. (2023). Recent pharmacological advances in the treatment of cardiovascular events with astragaloside IV. Biomedicine and Pharmacotherapy, 168, 115752.

    Article  CAS  PubMed  Google Scholar 

  19. Zhao, F., Meng, Y., & Wang, Y., et al. (2022). Protective effect of Astragaloside IV on chronic intermittent hypoxia-induced vascular endothelial dysfunction through the calpain-1/SIRT1/AMPK signaling pathway. Frontiers in Pharmacology, 13, 920977.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Su, Y., Yin, X., & Huang, X. (2022). Astragaloside IV ameliorates sepsis-induced myocardial dysfunction by regulating NOX4/JNK/BAX pathway. Life Sciences, 310, 121123.

    Article  CAS  PubMed  Google Scholar 

  21. Leng, B., Tang, F., & Lu, M., et al. (2018). Astragaloside IV improves vascular endothelial dysfunction by inhibiting the TLR4/NF-κB signaling pathway. Life Sciences, 209, 111–121.

    Article  CAS  PubMed  Google Scholar 

  22. Lin, L. H., Lee, H. P., & Yeh, M. L. (2020). Characterization of a sandwich PLGA-gallic acid-PLGA coating on Mg alloy ZK60 for bioresorbable coronary artery stents. Materials, 13, 5538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. You, L., Fang, Z., & Shen, G., et al. (2019). Astragaloside IV prevents high glucoseinduced cell apoptosis and inflammatory reactions through inhibition of the JNK pathway in human umbilical vein endothelial cells. Molecular Medicine Reports, 19, 1603–1612.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Xu, L., Willumeit-Romer, R., & Luthringer-Feyerabend, B. J. C. (2019). Effect of magnesium-degradation products and hypoxia on the angiogenesis of human umbilical vein endothelial cells. Acta Biomaterialia, 98, 269–283.

    Article  CAS  PubMed  Google Scholar 

  25. Li, L., Zhuang, S., & Jiang, S. (2024). Muscone inhibits the progression of atherosclerotic plaques in mice aorta by inhibiting the NF-κB/p65 pathway. Biochemical and Biophysical Research Communications, 702, 149628.

    Article  CAS  PubMed  Google Scholar 

  26. Becker, L. & Holtmann D. (2024). Anti-inflammatory effects of α-humulene on the release of pro-inflammatory cytokines in lipopolysaccharide-induced THP-1 cells. Cell Biochemistry and Biophysics, 82. https://doi.org/10.1007/s12013-024-01235-7.

  27. Thayse, K., Kindt, N., & Laurent, S. (2020). VCAM-1 target in non-invasive imaging for the detection of atherosclerotic plaques. Biology, 9(11), 1–22.

    Article  Google Scholar 

  28. Cheng, W., Cui, C., & Liu, G., et al. (2023). NF-κB, a potential therapeutic target in cardiovascular diseases. Cardiovascular Drugs and Therapy, 37(3), 571–584.

    Article  CAS  PubMed  Google Scholar 

  29. Nie, Q., Zhu, L., & Zhang, L., et al. (2019). Astragaloside IV protects against hyperglycemia-induced vascular endothelial dysfunction by inhibiting oxidative stress and Calpain-1 activation. Life Sciences, 232, 116662.

    Article  CAS  PubMed  Google Scholar 

  30. Shao, X., Liu, Z., & Liu, S., et al. (2021). Astragaloside IV alleviates atherosclerosis through targeting circ_0000231/miR-135a-5p/CLIC4 axis in AS cell model in vitro. Molecular and Cellular Biochemistry, 476, 1783–1795.

    Article  CAS  PubMed  Google Scholar 

  31. Zhang, Y., Du, M., & Wang, J., et al. (2022). Astragaloside IV relieves atherosclerosis and hepatic steatosis via MAPK/NF-κB signaling pathway in LDLR-/- Mice. Frontiers in Pharmacology, 13, 828161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the Shaanxi Provincial Department of Science and Technology (Grant numbers 2021JQ-738, 2021JM-549 and 2024JC-YBQN-0198), Education Department of Shaanxi Provincial Government (Grant number 21JK0606), Shaanxi Association for Science and Technology (Grant number 20200312). Author Hongfei Qi has received research support from Shaanxi University of Chinese Medicine.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were preformed by Hongfei Qi, Teng Ge, Kun Wang and **g Wang. The first draft of the manuscript was written by Hongfei Qi and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Lin Dang or Haifang Wang.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Consent for Publication

All the authors agreed on the publication of this manuscript.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qi, H., Ge, T., Wang, K. et al. Effect of High Magnesium and Astragaloside IV on Vascular Endothelial Cells. Cell Biochem Biophys (2024). https://doi.org/10.1007/s12013-024-01250-8

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12013-024-01250-8

Keywords

Navigation