Neurological Surgery 脳神経外科34巻2号

2006年02月発行

総説

血管新生研究と脳神経外科治療への展開

著者： 阿部竜也¹ 上田徹¹ 藤木稔¹ 古林秀則¹

所属機関： ¹大分大学医学部脳神経外科

ページ範囲：P.123 - P.132

Ⅰ．は じ め に

　血管新生を促進または抑制する作用を指標として，これまでにさまざまな因子が血管新生に関与することが報告された．特にVEGF（vascular endothelial growth factor, 血管内皮増殖因子）やアンジオポエチン（angiopoetin）といった血管内皮細胞に選択的に作用する分子が同定されたことによって，血管新生に関する研究はこの十年で飛躍的に進歩した．さらには血管内皮前駆細胞の発見以来，従来の既存血管内皮細胞の再形成（angiogenesis）の他に，血管内皮前駆細胞からの発生（vasculogenesis）のメカニズムが関与することが明らかになった．

　血管系は血管内皮細胞とその周囲の血管平滑筋細胞（末梢では周皮細胞）からなるが，近年これら血管系細胞の発生・分化・形体形成に関与する遺伝子群の同定も飛躍的に進み，シグナル伝達系や機能の解析もわかってきた．血管内皮細胞を誘導する因子としてVEGFとその受容体，動・静脈の分化に関与するエフリンB2とEphB4受容体システム，血管内皮細胞と平滑筋細胞の相互調節に関与するアンジオポエチン（angiopoetin）とTIE受容体システムなどさまざまな因子が複雑に絡み合いながら，血管新生に働いている．またこれらの諸因子は生理的な血管新生のみならず，腫瘍や炎症など病的血管新生にも関与している．血管新生と低酸素状態は密接な関係があるため，本稿では血管新生の概略を示し，低酸素状態における細胞のストレス応答と転写因子Hypoxia-inducible factor（HIF）に焦点をあて，治療への応用について概説する．

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