title: Amorphous nanosilica particles evoke vascular relaxation through PI3K/Akt/eNOS signaling.
abstract: There have been several reported studies on the distribution and/or toxicity of nanosilica particles. However, the influence of these particles on blood vessels through which they are distributed is poorly understood. Hence, we investigated the effects of nano- and micromaterials on blood vessel shrinkage and relaxation. Nanosilica particles with diameters of 70 nm (nSP70) were used as the nanomaterial, and particles of 300 and 1000 nm (nSP300 and mSP1000, respectively) were used as micromaterials. A rat thoracic aorta was used as the test blood vessel. The nano- and micromaterials had no effect on vessel shrinkage. Of the nano- and micromaterials tested, only nSP70 strongly evoked vascular relaxation. Vascular relaxation evoked by nSP70 was almost completely inhibited by the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin. In addition, the selective nitric oxide synthesis inhibitor NG-nitro-l-arginine methyl ester, which inhibits endothelial nitric oxide synthase (eNOS) downstream of PI3K signaling, inhibited vascular relaxation evoked by nSP70. In an analysis using bovine aortic endothelial cells (bAECs), nSP70 phosphorylated protein kinase B (AKT) and eNOS acted downstream of PI3K signaling. PI3K inhibition by wortmannin reduced AKT and eNOS phosphorylation. These results demonstrated that 70-nm amorphous nanosilica particles evoked vascular relaxation through PI3K/Akt/eNOS signaling. Moreover, it was suggested that nanomaterials, in general, control or disrupt vascular function by activating a known signal cascade.
authors.affiliation: Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, 650-8586, Japan. onodera@pharm.kobegakuin.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Onodera
authors.affiliation: Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, 650-8586, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yayama
authors.affiliation: Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, 650-8586, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, 650-8586, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Morosawa
authors.affiliation: Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, 650-8586, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Furuta
authors.affiliation: Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, 650-8586, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Takeda
authors.affiliation: Electron Microscope Laboratory, RIKEN Centre for Developmental Biology, 2-2-3 Minatojima Minami-Cho, Kobe, 650-0047, Japan.
authors.forename: Kisa
authors.initials: K
authors.lastname: Kakiguchi
authors.affiliation: Electron Microscope Laboratory, RIKEN Centre for Developmental Biology, 2-2-3 Minatojima Minami-Cho, Kobe, 650-0047, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.affiliation: Department of Developmental Medicine, Osaka Medical Centre and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Yanagihara
authors.affiliation: Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
authors.affiliation: Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, 650-8586, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kawai
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009924:Organ Culture Techniques; D010316:Particle Size; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012822:Silicon Dioxide / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012822:Silicon Dioxide
keywords: blood vessel; endothelial cells; nanosilica particle; vascular relaxation; vascular smooth muscle cells