Vascular endothelial growth factor-A inhibits EphB4 and stimulates delta-like ligand 4 expression in adult endothelial cells.
Vascular endothelial growth factor-A inhibits EphB4 and stimulates delta-like ligand 4 expression in adult endothelial cells.
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血管内皮生长因子A抑制EPHB4并刺激成人内皮细胞中的三角形的配体4表达。
DOI：
10.1016/j.jss.2013.01.009
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发表时间：
2013-07
影响因子：
2.2
通讯作者：
Dardik, Alan
中科院分区：
文献类型：
--
作者：
Yang, Chenzi;Guo, Yuanyuan;Jadlowiec, Caroline C.;Li, Xin;Lv, Wei;Model, Lynn S.;Collins, Michael J.;Kondo, Yuka;Muto, Akihito;Shu, Chang;Dardik, Alan
在静脉移植物适应动脉循环期间，血管内皮生长因子（VEGF）-A表达在下调之前短暂增加;然而，VEGF-A在静脉重塑中的作用尚不清楚。此外，尽管VEGF-A刺激新生动脉内皮细胞（EC）中的血管生成并决定动脉特性，但VEGF-A在成人静脉EC中调节特性的作用也不清楚。用VEGF-A（0- 100 ng/ml）刺激野生型（EphB 4 +/+）或杂合敲除（EphB 4 +/-）的EC，并用qPCR和蛋白质印迹法检查。VEGF-A（100 ng/ml）抑制EphB 4的表达并刺激dll 4的表达，但不刺激Notch或EphrinB 2的表达。用VEGFR 2中和抗体预处理消除了VEGF刺激的EphB 4的下调，但没有消除Dll 4的上调。用PD 98059或wortmannin预处理表明，VEGF-A下调EphB 4和上调dll 4是MEK-ERK依赖性的，但不依赖于PI 3 k-Akt。与对照EC中VEGF诱导的EphB 4下调和Dll 4上调相比，EphB 4 +/-EC中EphB 4信号传导的减少甚至进一步显示EphB 4的下调和dll 4的上调。尽管动脉和静脉EC命运的遗传编程，VEGF-A可以抑制成人静脉EC中的静脉身份，而不诱导动脉身份。体外成人EC的这些变化概括了体内静脉移植物适应动脉环境期间描述的身份变化。
During vein graft adaptation to the arterial circulation, vascular endothelial growth factor (VEGF)-A expression transiently increases before becoming down-regulated; however the role of VEGF-A in venous remodeling is not clear. In addition, although VEGF-A stimulates angiogenesis and determines arterial identity in nascent arterial endothelial cells (EC), the role of VEGF-A in regulating identity in adult venous EC is also not clear. EC, wild type (EphB4+/+) or heterozygous knockout (EphB4+/−), were stimulated with VEGF-A (0–100ng/ml) and examined with qPCR and Western blotting. VEGF-A (100ng/ml) inhibited expression of EphB4 and stimulated expression of dll4 but did not stimulate either notch or EphrinB2 expression in adult venous EC. Pretreatment with VEGFR2 neutralizing antibody abolished VEGF-stimulated down-regulation of EphB4 but not the up-regulation of Dll4. Pretreatment with PD98059 or wortmannin showed that VEGF-A down-regulation of EphB4 and up-regulation of dll4 are MEK-ERK-dependent but PI3k-Akt-independent. Compared to VEGF-induced EphB4 down-regulation and Dll4 up-regulation in control EC, reduced EphB4 signaling in EphB4+/− EC showed even further down-regulation of EphB4 and up-regulation of dll4. Despite the genetic programming of arterial and venous EC fate, VEGF-A can repress venous identity in adult venous EC without induction of arterial identity. These changes in adult EC in vitro recapitulate the changes in identity described during vein graft adaptation to the arterial environment in vivo.
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影响因子：
11.8
作者：
Lanahan, Anthony A.;Hermans, Karlien;Claes, Filip;Kerley-Hamilton, Joanna S.;Zhuang, Zhen W.;Giordano, Frank J.;Carmeliet, Peter;Simons, Michael
通讯作者：
Simons, Michael
DOI：
10.1016/j.jss.2011.06.036
发表时间：
2011-11
期刊：
The Journal of surgical research
影响因子：
--
作者：
Kondo Y;Muto A;Kudo FA;Model L;Eghbalieh S;Chowdhary P;Dardik A
通讯作者：
Dardik A
影响因子：
37.8
作者：
Hayashi, S;Asahara, T;Losordo, DW
通讯作者：
Losordo, DW
影响因子：
16
作者：
Gerety, SS;Wang, HU;Anderson, DJ
通讯作者：
Anderson, DJ
影响因子：
9
作者：
HENDERSON, VJ;MITCHELL, RS;MILLER, DC
通讯作者：
MILLER, DC