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イタノ ナオキ
ITANO NAOKI
板野 直樹 所属 京都産業大学 生命科学部 先端生命科学科 職種 教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2013/03/06 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | Crucial Role of Hyaluronan in Neointimal Formation after Vascular Injury |
| 執筆形態 | その他 |
| 掲載誌名 | PLoS ONE |
| 巻・号・頁 | 8(3),pp.e58760 |
| 著者・共著者 | Yuichiro Kashima,Masafumi Takahashi,Yuji Shiba,Naoki Itano,Atsushi Izawa,Jun Koyama,Jun Nakayama,Shun'ichiro Taniguchi,Koji Kimata,Uichi Ikeda |
| 概要 | Background: Hyaluronan (HA) is a primary component of the extracellular matrix of cells, and it is involved in the pathogenesis of atherosclerosis. The purpose of this study was to investigate the role of HA in neointimal formation after vascular injury and determine its tissue-specific role in vascular smooth muscle cells (VSMCs) by using a cre-lox conditional transgenic (cTg) strategy. Methods and Results: HA was found to be expressed in neointimal lesions in humans with atherosclerosis and after wire-mediated vascular injury in mice. Inhibition of HA synthesis using 4-methylumbelliferone markedly inhibited neointimal formation after injury. In vitro experiments revealed that low-molecular-weight HA (LMW-HA) induced VSMC activation, including migration, proliferation, and production of inflammatory cytokines, and reactive oxygen species (ROS). The migration and proliferation of VSMCs were mediated by the CD44/RhoA and CD44/ERK1/2 pathways, respectively. Because HA synthase 2 (HAS2) is predominantly expressed in injured arteries, we generated cTg mice that overexpress the murine HAS2 gene specifically in VSMCs (cHAS2/CreSM22α mice) and showed that HA overexpression markedly enhanced neointimal formation after cuff-mediated vascular injury. Further, HA-overexpressing VSMCs isolated from cHAS2/CreSM22α mice showed augmented migration, proliferation, and production of inflammatory cytokines and ROS. Conclusion: VSMC-derived HA promotes neointimal formation after vascular injury, and HA may be a potential therapeutic target for cardiovascular disease. © 2013 Kashima et al. |
| DOI | 10.1371/journal.pone.0058760 |
| ISSN | 1932-6203 |
| PMID | 23484050 |