Denizot Yves, Leguyader Alexandre, Cornu Elisabeth, Laskar Marc, Orsel Isabelle, Vincent Christelle, Nathan Nathalie
UMR CNRS 6101, Centre National de Recherche Scientifique, Université de Limoges, France.
J Cardiothorac Surg. 2007 Sep 21;2:38. doi: 10.1186/1749-8090-2-38.
This study was conducted to follow plasma concentrations of sFlt-1 and sKDR, two soluble forms of the vascular endothelial growth factor (VEGF) receptor in patients undergoing coronary artery bypass graft (CABG) surgery with extracorporeal circulation (ECC).
Plasma samples were obtained before, during and after surgery in 15 patients scheduled to undergo CABG. Levels of sFlt-1 and KDR levels were investigated using specific ELISA.
A 75-fold increase of sFlt-1 was found during cardiac surgery, sFlt-1 levels returning to pre-operative values at the 6th post-operative hour. In contrast sKDR levels did not change during surgery. The ECC-derived sFlt-1 was functional as judge by its inhibitory effect on the VEGF mitogenic response in human umbilical vein endothelial cells (HUVECs). Kinetic experiments revealed sFlt-1 release immediately after the beginning of ECC suggesting a proteolysis of its membrane form (mFlt-1) rather than an elevated transcription/translation process. Flow cytometry analysis highlighted no effect of ECC on the shedding of mFlt-1 on platelets and leukocytes suggesting vascular endothelial cell as a putative cell source for the ECC-derived sFlt-1.
sFlt-1 is released during CABG with ECC. It might be suggested that sFlt-1 production, by neutralizing VEGF and/or by inactivating membrane-bound Flt-1 and KDR receptors, might play a role in the occurrence of post-CABG complication.
本研究旨在追踪接受体外循环（ECC）冠状动脉旁路移植术（CABG）患者血浆中血管内皮生长因子（VEGF）受体的两种可溶性形式，即可溶性fms样酪氨酸激酶-1（sFlt-1）和可溶性激酶插入结构域受体（sKDR）的浓度。
在15例计划接受CABG手术的患者术前、术中和术后采集血浆样本。使用特异性酶联免疫吸附测定（ELISA）法检测sFlt-1和sKDR水平。
心脏手术期间发现sFlt-1增加了75倍，术后第6小时sFlt-1水平恢复到术前值。相比之下，sKDR水平在手术期间未发生变化。通过其对人脐静脉内皮细胞（HUVECs）中VEGF促有丝分裂反应的抑制作用判断，ECC衍生的sFlt-1具有功能活性。动力学实验显示，ECC开始后立即释放sFlt-1，提示其膜形式（mFlt-1）发生蛋白水解，而非转录/翻译过程增强。流式细胞术分析表明，ECC对血小板和白细胞上mFlt-1的脱落无影响，提示血管内皮细胞可能是ECC衍生sFlt-1的假定细胞来源。
CABG联合ECC手术期间会释放sFlt-1。可以推测，sFlt-1的产生可能通过中和VEGF和/或使膜结合的Flt-1和KDR受体失活，在CABG术后并发症的发生中发挥作用。
