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

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 MgCl 2 solutions were prepared to study their effect on macrophages. To study the effects of the JDBM extracts and MgCl 2 solutions on the function of VSMCs via immunoregulation of macrophages, conditioned media (CM) obtained from macrophages was used to establish a VSMCmacrophage indirect coculture system.Results: Our results showed that both JDBM extracts and MgCl 2 solutions significantly attenuated the inflammatory response stimulated by lipopolysaccharide (LPS)-activated macrophages and converted macrophages into M2-type cells. In addition, JDBM extracts and MgCl 2 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 + MgCl 2 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.

Immune response differences in degradable and non-degradable alloy implants

“…This low intracellular Ca halts the activation of phagocytic cells and cytokine production which reduces the inflammation [ 130 ]. down-regulate the production of M1-like and up-regulate M2-like macrophage-related cytokines, and as a result, rapid inflammation resolution and tissue repair can occur [ 57 , 131 , 132 ]. Examples of Mg Alloys interaction RS66 alloy (Mg-6.0Zn-1.0Y-0.6Ce-0.6Zr) No acute inflammation [ 133 ].…”

“…down-regulate the production of M1-like and up-regulate M2-like macrophage-related cytokines, and as a result, rapid inflammation resolution and tissue repair can occur [ 57 , 131 , 132 ].…”

IL-1β promotes A7r5 and HASMC migration and invasion via the p38-MAPK/Angpt-2 pathway

“…The accumulation of lipids and inflammatory cells in the blood vessel wall is the main feature of CAS. Inflammatory cells accumulate in the arterial wall and promote the proliferation and migration of VSMC cells by secreting inflammatory factors and expressing proteins [ 7 – 9 ]. Previous studies confirmed that the pro-inflammatory properties of IL-1β are related to the development of CAS lesions.…”

IL-1β Promotes A7r5 and HASMC Migration and Invasion via the p38-MAPK/Ang2 Pathway

“…In ammatory cells accumulate in the arterial wall and promote the proliferation and migration of VSMC cells by secreting in ammatory factors and expressing proteins [7][8][9] . Previous studies con rmed that the pro-in ammatory properties of IL-1β are related to the development of CAS lesions.…”