Critical role of hyalurona derived from vascular smooth muscle cells after vascular injury in mice

血管平滑肌细胞来源的透明质酸在小鼠血管损伤后的关键作用

• 批准号: 23790843
• 负责人: KASHIMA Yuichiro
• 金额: $ 2.75万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790843/
• 关键词: ヒアルロン酸; 血管平滑筋細胞; 動脈硬化; マクロファージ; ステント内再狭窄; 血管平滑筋

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 vascular smooth muscle cells (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/CreSM22 alpha mice) and showed that HA overexpression markedly enhanced neointimal formation after cuff-mediated vascular injury. Further, HA-overexpressing VSMCs isolated from cHAS2/CreSM22alpha mice showed augmented migration, proliferation, and production of inflammatory cytokines and ROS.

使用4-甲基伞形酮抑制HA合成可显著抑制损伤后新生内膜形成。体外实验表明，低分子量HA（LMW-HA）诱导血管平滑肌细胞（VSMC）活化，包括迁移，增殖，产生炎性细胞因子和活性氧（ROS）。CD 44/RhoA和CD 44/ERK 1/2通路分别介导VSMCs的迁移和增殖。由于HA合酶2（HAS 2）主要在受损的动脉中表达，因此我们产生了在VSMC中特异性过表达鼠HAS 2基因的cTg小鼠（cHAS 2/CreSM 22 α小鼠），并显示HA过表达显著增强了袖套介导的血管损伤后的新生内膜形成。此外，从cHAS 2/CreSM 22 α小鼠中分离的HA过表达VSMC显示出增强的迁移、增殖和炎性细胞因子和ROS的产生。

项目成果

Crucial role of hyaluronan derived from macrophages in neointimal formation after vascular injury.

源自巨噬细胞的透明质酸在血管损伤后新内膜形成中的关键作用。

• 发表时间: 2013
• 作者: Kashima Y;Takahashi M;Itano N;Taniguchi S;Kimata K;Ikeda U.
• 通讯作者: Ikeda U.

LV dysfunction caused by persistent atrial fibrillation was associated with high reactive oxidative metabolities in coronary sinus vein

持续性心房颤动引起的左心室功能障碍与冠状窦静脉的高反应性氧化代谢相关

• 发表时间: 2012
• 作者: Okada A;Tomita T;Kashima Y;Oguchi Y;Takeuchi T;Aizawa K;Ikeda U
• 通讯作者: Ikeda U

The impact of mesurement of reactive oxygen species (ROS) and hydroxyl radicals (-OH) in the pasients of peripheral artery disease.

活性氧（ROS）和羟自由基（-OH）测定对外周动脉疾病患者的影响。

• 发表时间: 2011
• 作者: Miyashita Y;Kashima Y;Kumazaki S;Aso S;Otagiri K;Saigusa T;Koyama J;Ikeda U.
• 通讯作者: Ikeda U.

Crucial role of hyaluronan in neointimal formation after vascular injury.

• DOI: 10.1371/journal.pone.0058760
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kashima Y;Takahashi M;Shiba Y;Itano N;Izawa A;Koyama J;Nakayama J;Taniguchi S;Kimata K;Ikeda U
• 通讯作者: Ikeda U

Lv remodeling caused by persistent AF was associated with high cardiac hyaluronan in Cs vein

持续性房颤引起的左室重塑与 Cs 静脉中高心脏透明质酸相关

• 发表时间: 2013
• 作者: Okada A;Tomita T;Kashima Y;Yoshie K;Takeuchi T;Ikeda U
• 通讯作者: Ikeda U