文献类型：会议

作　　者：路瑶 熊彦 霍迎庆 韩晶岩 杨晓 张荣利 朱德生 Stefan Klein-Heβling 李军 张小玉 韩晓帆 李艳丽 沈兵 何玉龙 Masabumi Shibuya 冯更生 罗金才

作者单位：[1]北京大学分子医学研究所血管生物学研究室 [2]北京大学天士力微循环中心 [3]解放军军事医学科学院

会议文献：“细胞活动 生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会论文摘要集

会议名称：“细胞活动 生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会

会议日期：20110716

会议地点：中国北京

主办单位：中国细胞生物学学会（Chinese Society for Cell Biology）

出版日期：20110716

学会名称：中国细胞生物学学会

语　　种：中文

摘　　要：The intracellular signaling mechanisms underlying postnatal angiogenesis are incompletely understood.Herein we show that Grb-2-associated binder 1(Gab1) plays a critical role in ischemic and VEGF-induced angiogenesis.Endothelium-specific Gab1 knockout(EGKO) mice displayed impaired angiogenesis in the ischemic hindlimb despite normal induction of VEGF expression.Matrigel plugs with VEGF implanted in EGKO mice induced fewer capillaries than those in control mice.The vessels and endothelial cells(ECs) derived from EGKO mice were defective in vascular sprouting and tube formation induced by VEGF.Biochemical analyses revealed a substantial reduction of eNOS activation in Gab1-deficient vessels and ECs following VEGF stimulation.Interestingly,the phosphorylation of Akt,an enzyme known to promote VEGF-induced eNOS activation,was increased in Gab1-deficient vessels and ECs whereas PKA activity was significantly decreased.Introduction of an active form of PKA rescued VEGF-induced eNOS activation and tube formation in EGKO ECs.Re-expression of wild type or mutant Gab1 molecules in EGKO ECs revealed requirement of Gab1/Shp2 association for the activation of PKA and eNOS.Taken together,these results identify Gab1 as a critical upstream signaling component in VEGF-induced eNOS activation and tube formation,which is dependent on PKA.Of note,this pathway is conserved in primary human ECs for VEGF-induced eNOS activation and tube formation,suggesting considerable potential in treatment of human ischemic diseases.

关 键 词：VEGF Gab1  

分 类 号：R363]