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

• Project/Area Number: 23790843
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: Shinshu University
• Principal Investigator: KASHIMA Yuichiro 信州大学, 医学部附属病院, 助教(診療) (70545722)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 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

Research Abstract

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.

Research Products

• [Journal Article] Crucial role of hyaluronan in neointimal formation after vascular injury. (2013)
  • Author(s): Kashima Y, Takahashi M, Shiba Y, Itano N, Izawa A, Koyama J, Nakayama J, Taniguchi S, Kimata K, Ikeda U.
  • Journal Title: PLoS One Volume: 8 Issue: 3 Pages: e58760-e58760
  • DOI: 10.1371/journal.pone.0058760
  • Peer Reviewed
• [Journal Article] Immunoadsorption therapy reduces oxidative stress in patients with dilated cardiomyopathy. (2012)
  • Author(s): Kasai H, Kashima Y, Izawa A, Tomita T, Miyashita Y, Koyama J, Takahashi M, Yoshio T, Yazaki Y, Higuchi M, Ikeda U
  • Journal Title: WJCD Volume: 2 Issue: 04 Pages: 305-312
  • DOI: 10.4236/wjcd.2012.24048
  • Peer Reviewed
• [Presentation] Critical role of hyaluronan derived from macrophages in neointimal formation after vascular injury in mice (2013)
  • Author(s): Kashima Y, Takahashi M, Kimata K, Itano N, Ikeda U
  • Organizer: AHA2013アメリカ心臓協会
  • Place of Presentation: ダラス(アメリカ)
• [Presentation] Lv remodeling caused by persistent AF was associated with high cardiac hyaluronan in Cs vein (2013)
  • Author(s): Okada A, Tomita T, Kashima Y, Yoshie K, Takeuchi T, Ikeda U
  • Organizer: AHA2013アメリカ心臓協会
  • Place of Presentation: ダラス(アメリカ)
• [Presentation] Crucial role of hyaluronan derived from macrophages in neointimal formation after vascular injury (2013)
  • Author(s): Kashima Y, Takahashi M, Itano N, Taniguchi S, Kimata K, Ikeda U
  • Organizer: ESC2013欧州心臓学会議
  • Place of Presentation: アムステルダム(オランダ)
• [Presentation] Crucial role of hyaluronan derived from macrophages in neointimal formation after vascular injury. (2013)
  • Author(s): Kashima Y, Takahashi M, Itano N, Taniguchi S, Kimata K, Ikeda U.
  • Organizer: 欧州心臓学会議
  • Place of Presentation: アムステルダム（オランダ）
• [Presentation] Critical role of hyaluronan derived from macrophages in neointimal formation after vascular injury in mice. (2013)
  • Author(s): Kashima Y, Takahashi M, Kimata K, Itano N, Ikeda U.
  • Organizer: 米国心臓病学会議
  • Place of Presentation: ダラス（アメリカ）
• [Presentation] Critical role of hyaluronan in neointimal formation after vascular injury in mice (2012)
  • Author(s): Kashima Y, Takahashi M, Shiba Y, Itano N, Kimata K, Izawa A, Ikeda U
  • Organizer: AHA2012アメリカ心臓協会
  • Place of Presentation: ロサンゼルス(アメリカ)
• [Presentation] LV dysfunction caused by persistent atrial fibrillation was associated with high reactive oxidative metabolities in coronary sinus vein (2012)
  • Author(s): Okada A, Tomita T, Kashima Y, Oguchi Y, Takeuchi T, Aizawa K, Ikeda U
  • Organizer: ESC2012欧州心臓学会議
  • Place of Presentation: ミュンヘン(ドイツ)
• [Presentation] 心房細動の持続に伴う左室機能障害は、冠状静脈における酸化ストレスの上昇と関連性を認め、アブレーション治療後血中酸化ストレスは有意に改善する (2012)
  • Author(s): 岡田綾子、富田威、嘉嶋勇一郎、小口泰尚、竹内崇博、相澤万象、池田宇一
  • Organizer: 第27回日本不整脈学会学術大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Critical role of NFκB p65 in pathogenesis of spontaneous in p50 deficient mice (2012)
  • Author(s): Gautam M, Izawa A, Shiba Y, Kashima Y, Koyama J, Hongo M, Sano K, Hayashi T, Ichikawa M, Ikeda U
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] Critical role of hyaluronan in neointimal formation after vascular injury in mice. (2012)
  • Author(s): Kashima Y, Takahashi M, Shiba Y, Itano N, Kimata K, Izawa A, Ikeda U
  • Organizer: 米国心臓病学会議
  • Place of Presentation: ロサンゼルス
• [Presentation] Critical Role of Hyaluronan Derived From Vascular Smooth Muscle Cells in Neointimal Formation After Vascular Injury (2011)
  • Author(s): Kashima Y, Takahashi M, Hata T, Kawaguchi M, Izawa A, Itano N, Taniguchi S, Ikeda U
  • Organizer: AHA2011アメリカ心臓協会
  • Place of Presentation: オーランド(アメリカ)
• [Presentation] Specific Overexpression of Hyaluronan in Vascular Smooth Muscle Cells Augments Neointimal Formation after Vascular Injury in Mice (2011)
  • Author(s): Kashima Y, Takahashi M, Hata T, Kawaguchi M, Izawa A, Itano N, Kimata K, Ikeda U
  • Organizer: 第75回日本循環器学会
  • Place of Presentation: 横浜
• [Presentation] The impact of mesurement of reactive oxygen species (ROS) and hydroxyl radicals (-OH) in the pasients of peripheral artery disease (2011)
  • Author(s): Miyashita Y, Kashima Y, Kumazaki S, Aso S, Otagiri K, Saigusa T, Koyama J, Ikeda U
  • Organizer: 第20回日本心血管インターベンション治療学会
  • Place of Presentation: 大阪
• [Presentation] Critical Role of Hyaluronan Derived From Vascular Smooth Muscle Cells in Neointimal Formation After Vascular Injury (2011)
  • Author(s): 嘉嶋 勇一郎
  • Organizer: American Heart Association Scientific Sessionn
  • Place of Presentation: オーランド（アメリカ）
• [Presentation] The impact of mesurement of reactive oxygen species (ROS) and hydroxyl radicals (-OH) in the pasients of peripheral artery disease. (2011)
  • Author(s): Miyashita Y, Kashima Y, Kumazaki S, Aso S, Otagiri K, Saigusa T, Koyama J, Ikeda U.
  • Organizer: 第20回日本心血管インターベンション治療学会
  • Place of Presentation: 大阪
• [Presentation] Specific Overexpression of Hyaluronan in Vascular Smooth Muscle Cells Augments Neointimal Formation after Vascular Injury in Mice. (2011)
  • Author(s): Kashima Y, Takahashi M, Hata T, Kawaguchi M, Izawa A, Itano N, Kimata K, Ikeda U.
  • Organizer: 第75回日本循環器学会
  • Place of Presentation: 横浜