Epac1 promotes neointimal thickening via calcium/calcineurin-dependent smooth muscle cell polarization and migration after vascular injury.

Epac1 通过血管损伤后钙/钙调磷酸酶依赖性平滑肌细胞极化和迁移促进新生内膜增厚。

• 批准号: 24790558
• 负责人: KATO Yuko
• 金额: $ 2.83万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790558/
• 关键词: 血管内膜肥厚; Epac1

Vascular remodeling after mechanoinjury largely depends on migration of aortic smooth muscle cell (ASMC). We have reported that activation of exchange protein activated by cAMP 1 (Epac1) promotes ASMC migration. However, the role of Epac1 in advancing vascular remodeling upon vascular injury in vivo, and the intracellular mechanisms remain unknown.PDGF-BB-induced directional migration of Epac1KO ASMCs was significantly decreased. PDGF-BB-mediated intracellular Ca2+ elevation of Epac1KO ASMCs was significantly reduced. To assess the establishment of cell polarization under stimulation with PDGF-BB,activation of cofilin in Epac1KO ASMCs was significantly degreased. Activation of cofilin in WT ASMCs was suppressed by cyclosporine A, a calcineurin inhibitor. Ratio intimal thickening to smooth muscle layer of Epac1KO was significantly lower than that of WT.These results suggest that Epac1 promotes directional migration of ASMC via calcium/calcineurin-mediated activation of cofilin.

机械性损伤后的血管重构主要依赖于主动脉平滑肌细胞（ASMC）的迁移。我们已经报道了由cAMP 1激活的交换蛋白（Epac 1）的激活促进ASMC迁移。Epac1在体内血管损伤后促进血管重构的作用及其细胞内机制尚不清楚，PDGF-BB诱导的Epac1KO ASMCs定向迁移明显减少。PDGF-BB介导的Epac1KO ASMCs细胞内Ca2+升高显著降低。为了评估在用PDGF-BB刺激下细胞极化的建立，Epac1KO ASMC中的cofilin的活化被显著地降低。WT ASMCs中cofilin的激活被钙调磷酸酶抑制剂环孢素A抑制。Epac1KO的内膜增厚与平滑肌层的比率显著低于WT。这些结果表明Epac1通过钙/钙调神经磷酸酶介导的cofilin激活促进ASMC的定向迁移。

项目成果

Epac1 promotes smooth muscle cell migration via calcium/calcineurin-dependent cell polarization

Epac1 通过钙/钙调磷酸酶依赖性细胞极化促进平滑肌细胞迁移

• 发表时间: 2013
• 作者: Kato Y;Yokoyama U;Okumura S;Minamisawa S;Ishikawa S
• 通讯作者: Ishikawa S

Epac1 promotes smooth muscle cell migration via calcium/calcineurin-dependent cell polarization.

Epac1 通过钙/钙调磷酸酶依赖性细胞极化促进平滑肌细胞迁移。

• 发表时间: 2013
• 作者: Yuko Kato Utako Yokoyama;Satoshi Okumura;Susumu Minamisawa;Yoshihiro Ishikawa
• 通讯作者: Yoshihiro Ishikawa