Increased vascular permeability after cardiopulmonary bypass in patients with diabetes is associated with increased expression of vascular endothelial growth factor and hepatocyte growth factor.
Increased vascular permeability after cardiopulmonary bypass in patients with diabetes is associated with increased expression of vascular endothelial growth factor and hepatocyte growth factor.
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DOI：
10.1016/j.jtcvs.2008.12.024
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发表时间：
2009-07
影响因子：
6
通讯作者：
Sellke, Frank W.
中科院分区：
文献类型：
--
作者：
Emani, Sirisha;Ramlawi, Basel;Sodha, Neel R.;Li, Jian;Bianchi, Cesario;Sellke, Frank W.
已知几种炎症介质如血管内皮生长因子（VEGF）和肝细胞生长因子（HGF）在调节血管通透性和血管生成中起关键作用。我们研究了糖尿病（DM）和非糖尿病（ND）患者体外循环（CPB）和心脏停搏（C）后外周血中生长因子的血清水平和参与生长因子信号传导的基因表达谱。从接受冠状动脉旁路移植术（CABG）的DM和匹配的ND患者（各n=7例）的血液样本中采集血清和总RNA; CPB/C前（前），CPB/C后6小时（6小时）和CPB/C后4天（4天）。使用多重细胞因子定量系统定量DM和ND患者CPB/C前、CPB/C后6 h和4 d的细胞因子组，包括生长因子，如VEGF、HGF、FGF和EGF。进行cDNA微阵列分析并计算倍数变化。与ND患者相比，DM患者的住院时间（10 vs. 6天; p= 0. 04）和体重增加（5 vs. 2. 5 kg; p= 0. 001）显著更长。与ND患者相比，DM患者CPB/C前与CPB/C后6 h的血清VEGF和HGF水平显著升高。此外，仅在DM患者中观察到CPB/C后4d HIF 1 α、CREB和EP 300的mRNA表达显著升高（> 2倍）。DM与ND患者中生长因子及其相关基因的基因和蛋白表达差异可能与CPB/C后DM患者水肿和体重增加增加有关。
Several inflammatory mediators such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are known to play a critical role in the regulation of vascular permeability and angiogenesis. We studied the serum levels of growth factors and gene expression profiles of genes involved in the growth factor signaling in the peripheral blood of diabetic (DM) and non-diabetic (ND) patients following cardiopulmonary bypass (CPB) and cardioplegic-arrest (C). Serum and total RNA were obtained from the blood samples collected from DM and matched ND patients (n=7 patients each) who underwent coronary artery bypass graft (CABG); before (pre), 6-hours (6h), and 4-days (4d) after CPB/C. The cytokine panel consisting of growth factors such as VEGF, HGF, FGF, and EGF was quantified in DM and ND patients; pre, 6h, and 4d post-CPB/C using multiplex cytokine quantification system. cDNA microarray analysis was performed and fold-change was calculated. Length of hospitalization (10 vs. 6 days; p=0.04) and weight gain (5 vs. 2.5 kg; p=0.001) were significantly greater for DM compared to ND patients. The serum levels of VEGF and HGF were significantly elevated in DM patients when compared to ND patients; pre vs. 6h post-CPB/C. In addition, significantly elevated mRNA expression of HIF1α, CREB, and EP300 (> 2 fold) was observed, 4d post-CPB/C exclusively in DM patients. The differential profile of gene and protein expression of growth factors and their related genes in DM vs. ND patients could be associated with increased edema and weight gain in DM patients after CPB/C.
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