The effects of a biodegradable Mg-based alloy on the function of VSMCs via immunoregulation of macrophages through Mg-induced responses
Open accessAbstract
Background: Restenosis is one of the worst side effects of percutaneous coronary intervention (PCI) due to neointima formation resulting from the excessive proliferation and migration of vascular smooth muscle cells (VSMCs) and continuous inflammation. Biodegradable Mg-based alloy is a promising candidate material because of its good mechanical properties and biocompatibility, and biodegradation of cardiovascular stents. Although studies have shown reduced neointima formation after Mg-based CVS implantation in vivo, these findings were inconsistent with in vitro studies, demonstrating magnesium-mediated promotion of the proliferation and migration of VSMCs. Given the vital role of activated macrophage-driven inflammation in neointima formation, along with the well-demonstrated crosstalk between macrophages and VSMCs, we investigated the interactions of a biodegradable Mg-Nd-Zn-Zr alloy (denoted JDBM), which is especially important for cardiovascular stents, with VSMCs via macrophages. Methods: JDBM extracts and MgCl2 solutions were prepared to study their effect on macrophages. To study the effects of the JDBM extracts and MgCl2 solutions on the function of VSMCs via immunoregulation of macrophages, conditioned media (CM) obtained from macrophages was used to establish a VSMC-macrophage indirect coculture system. Results: Our results showed that both JDBM extracts and MgCl2 solutions significantly attenuated the inflammatory response stimulated by lipopolysaccharide (LPS)-activated macrophages and converted macrophages into M2-type cells. In addition, JDBM extracts and MgCl2 solutions significantly decreased the expression of genes related to VSMC phenotypic switching, migration, and proliferation in macrophages. Furthermore, the proliferation, migration, and proinflammatory phenotypic switching of VSMCs were significantly inhibited when the cells were incubated with CMs from macrophages treated with LPS + extracts or LPS + MgCl2 solutions. Conclusions: Taken together, our results suggested that the magnesium in the JDBM extract could affect the functions of VSMCs through macrophage-mediated immunoregulation, inhibiting smooth muscle hyperproliferation to suppress restenosis after implantation of a biodegradable Mg-based stent.
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The ARG1 upregulation in the bare Mg group is likely attributable to localized release of H2 and Mg2+ that can mediate anti-inflammatory gene expression.
“likely attributable to localized release of H2 and Mg2+ that can mediate anti-inflammatory gene expression [63,64].”
From Nanocatalytic magnesium osteoimplants with biodegradable self-adaptive interfaces for therapeutic repair of infected bone defects (2026) · cites this paper as [64]
The Results section on macrophage polarization (page unavailable) reports that JDBM extracts and MgCl2 increased M2-associated gene expression and reduced proinflammatory gene expression, supporting the Mg2+ part of the explanation. It does not report H2-mediated expression or test ARG1 upregulation in a bare Mg group. (LLM, conf=0.87)
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- Authors
- Wu, J., Jin, L., Tan, J.-Y., Chen, X.-F., Wang, Q.-Q., Yuan, G.-Y., & Chen, T.-X.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Zhejiang Chinese Medical University (CN)
- Corresponding author
- Chen, Tong-Xin
- Venue
- Annals of Translational Medicine
- Publisher
- AME Publishing Company
- Published
- 2021-08
- Volume
- 9
- Issue
- 16
- Pages
- 1292-1292
- ISSN
- 2305-5839 (ISSN-L)
- 2305-5847
- PMC
- PMC8422083
- OpenAlex
- W3191804017
- Cited by
- 17
- References
- 57
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 6
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Update notices
- erratum (2022-09-01)
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Annals of Translational Medicine (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Massachusetts Department of Agricultural Resources
- National Natural Science Foundation of China (51701041, 81701626, 81871303, U1804251)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Magnesium Alloys: Properties and Applications
- Health Sciences › Medicine › Surgery › Coronary Interventions and Diagnostics
- Physical Sciences › Materials Science › Materials Chemistry › Titanium Alloys Microstructure and Properties
- Keywords
- biodegradable magnesium alloys, Mg-Nd-Zn-Zr alloy, vascular smooth muscle cells, macrophages, restenosis, percutaneous coronary intervention, cardiovascular stents, neointima formation, macrophage polarization, M2 macrophages, immune regulation, inflammation, lipopolysaccharide
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