title: Nickel-free stainless steel avoids neointima formation following coronary stent implantation.
abstract: SUS316L stainless steel and cobalt-chromium and platinum-chromium alloys are widely used platforms for coronary stents. These alloys also contain nickel (Ni), which reportedly induces allergic reactions in some subjects and is known to have various cellular effects. The effects of Ni on neointima formation after stent implantation remain unknown, however. We developed coronary stents made of Ni-free high-nitrogen austenitic stainless steel prepared using a N2-gas pressurized electroslag remelting (P-ESR) process. Neointima formation and inflammatory responses following stent implantation in porcine coronary arteries were then compared between the Ni-free and SUS316L stainless steel stents. We found significantly less neointima formation and inflammation in arteries implanted with Ni-free stents, as compared to SUS316L stents. Notably, Ni2+was eluted into the medium from SUS316L but not from Ni-free stainless steel. Mechanistically, Ni2+increased levels of hypoxia inducible factor protein-1α(HIF-1α) and its target genes in cultured smooth muscle cells. HIF-1αand their target gene levels were also increased in the vascular wall at SUS316L stent sites but not at Ni-free stent sites. The Ni-free stainless steel coronary stent reduces neointima formation, in part by avoiding activation of inflammatory processes via the Ni-HIF pathway. The Ni-free-stainless steel stent is a promising new coronary stent platform.
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, 113-8655, Tokyo, Japan; Translational Systems Biology and Medicine Initiative (TSBMI), University of Tokyo, Graduate School of Medicine, Tokyo, Japan.
authors.forename: Katsuhito
authors.initials: K
authors.lastname: Fujiu
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, 113-8655, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Manabe
authors.affiliation: Graduate School of Pure and Applied Science, University of Tsukuba, Tsukuba, Japan; Biomaterials Unit, Nano-Bio Field, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, Tsukuba, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Biomaterials Unit, Nano-Bio Field, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, Tsukuba, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, 113-8655, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwata
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, 113-8655, Tokyo, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Hasumi
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, 113-8655, Tokyo, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.affiliation: Biomaterials Unit, Nano-Bio Field, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, Tsukuba, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Katada
authors.affiliation: Graduate School of Pure and Applied Science, University of Tsukuba, Tsukuba, Japan; Biomaterials Unit, Nano-Bio Field, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, Tsukuba, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Taguchi
authors.affiliation: Jichi Medical University, Tochigi, Japan.
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
keywords: coronary; neointima; nickel free; stainless steel; stent