The effects of a biodegradable Mg-based alloy on the function of VSMCs via immunoregulation of macrophages through Mg-induced responses

Jing Wu; Liang Jin; Jin-Yun Tan; Xia-Fang Chen; Qing-Quan Wang; Guang-Yin Yuan; Tong-Xin Chen

doi:10.21037/atm-21-1375

The effects of a biodegradable Mg-based alloy on the function of VSMCs via immunoregulation of macrophages through Mg-induced responses

Ann Transl Med. 2021 Aug;9(16):1292. doi: 10.21037/atm-21-1375.

Authors

Jing Wu^{1

2

3}, Liang Jin^{1

3

4

5}, Jin-Yun Tan⁶, Xia-Fang Chen^{1

7}, Qing-Quan Wang⁸, Guang-Yin Yuan^{5

9}, Tong-Xin Chen^{1

2

3}

Affiliations

¹ Division of Immunology, Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Allergy/Immunology Innovation Team, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Rheumatology/Immunology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁴ College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
⁵ School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
⁶ Department of Vascular Surgery, Huashan Hospital of Fudan University, Shanghai, China.
⁷ Department of Neonatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁸ The Fifth People's Hospital of Wuhu, Anhui, China.
⁹ National Engineering Research Center of Light Alloys Net Forming and State Key Laboratory of Metal Matrix Composite, Shanghai Jiao Tong University, Shanghai, China.

Abstract

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.

Keywords: Biodegradable Mg-based alloy; JDBM magnesium alloy; immunoregulation; macrophage; vascular smooth muscle cells (VSMCs).