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大学・研究所にある論文を検索できる 「Important Role of Concomitant Lymphangiogenesis for Reparative Angiogenesis in Hindlimb Ischemia」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
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Important Role of Concomitant Lymphangiogenesis for Reparative Angiogenesis in Hindlimb Ischemia

Pu, Zhongyue Shimizu, Yuuki Tsuzuki, Kazuhito Suzuki, Junya Hayashida, Ryo Kondo, Kazuhisa Fujikawa, Yusuke Unno, Kazumasa Ohashi, Koji Takefuji, Mikito Bando, Yasuko K. Ouchi, Noriyuki Calvert, John W. Shibata, Rei Murohara, Toyoaki 名古屋大学

2021.06

概要

Objective:
Lymphatic vessels are distributed throughout the body and tightly collaborate with blood vessels to maintain tissue homeostasis. However, the functional roles of lymphangiogenesis in the process of reparative angiogenesis in ischemic tissues are largely unknown. Accordingly, we investigated potential roles of lymphangiogenesis using a mouse model of ischemia-induced angiogenesis.

Approach and Results:
Male C57BL/6J mice were subjected to unilateral hindlimb ischemia, in which not only angiogenesis but also lymphangiogenesis was induced. Next, the excessive and prolonged tissue edema model significantly deteriorated reparative angiogenesis and blood perfusion recovery in ischemic limbs. Finally, implantation of adipose-derived regenerative cells augmented ischemia-induced lymphangiogenesis, which was accompanied by reduced tissue edema and inflammation, resulting in improving reparative angiogenesis and blood perfusion recovery. In addition, inhibition of lymphangiogenesis by MAZ51, a specific VEGFR3 (vascular endothelial cell growth factor receptor 3) inhibitor, resulted in enhanced inflammatory cell infiltration, gene expression of TNF (tumor necrosis factor)-α, IL (interleukin)-1β, IL-6, TGF (transforming growth factor)-β, angiostatin, vasohibin, and endostatin, and tissue edema, resulting in reduced angiogenesis.

Conclusions:
The lymphatic system may have a clearance role of tissue edema and inflammation, which contribute to functional reparative angiogenesis in response to tissue ischemia. Modulation of lymphangiogenesis would become a novel therapeutic strategy for severe ischemic disease in addition to ordinary vascular intervention and therapeutic angiogenesis.

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