Insulin-like growth factor-1 induces phosphorylation of PI3K-Akt/PKB to potentiate proliferation of smooth muscle cells in human saphenous vein.
Insulin-like growth factor-1 induces phosphorylation of PI3K-Akt/PKB to potentiate proliferation of smooth muscle cells in human saphenous vein.
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DOI：
10.1016/j.yexmp.2010.04.002
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发表时间：
2010-08
影响因子：
3.6
通讯作者：
Agrawal, Devendra K.
中科院分区：
文献类型：
--
作者：
Jia, Guanghong;Mitra, Amit K.;Gangahar, Deepak M.;Agrawal, Devendra K.
关键词：
对于反复心肌缺血的患者，推荐通过冠状动脉旁路移植术（CABG）进行冠状动脉血运重建。然而，与乳内动脉（IMA）移植物相比，使用隐静脉（SV）移植物的CABG的长期结果并不令人满意。SV移植物失效是由于内膜增生的发展，这是一个以静脉移植物内膜层中平滑肌细胞（SMC）的异常迁移和增殖为特征的过程。胰岛素生长因子1（IGF-1）是一种主要的促有丝分裂生长因子，在剪切应力诱导的移植物损伤部位释放。本研究首次比较了分离的人旁路移植物导管中IGF-1-PI 3 K-Akt活化的程度。收集人SV和IMA血管，分离并培养SMCs。在培养的SMCs中，通过Western印迹分析检测IGF-1对总的和磷酸化的PI 3 K、Akt和IGF-1 R的影响。使用BrdU ELISA测量细胞增殖。人旁路管道中SV和IMA SMC磷酸化PI 3 K、Akt和IGF-1 R的基础表达无显著差异。然而，我们观察到IGF-1受体在SV SMC中的上调响应于IGF-1刺激，而在IMA SMC中没有作用。此外，免疫印迹和细胞信号激活ELISA（CASE）测定表明，IGF-1刺激的SV SMC中PI 3 K和Akt的活性均显著高于IMA。这被IGF-1 R阻断抗体抑制。IGF-1诱导的SV和IMA SMCs增殖可被PI 3 K抑制剂wortmannin抑制。这些数据证明了IGF-1诱导的PI 3 K-Akt活化的差异活性，其在SV SMC中比在IMA中在数量上和时间上更大。这至少可以部分解释冠状动脉旁路移植术后SV导管比IMA更容易发生内膜增生。
Coronary revascularization by coronary artery bypass grafting (CABG) is recommended in patients with recurrent myocardial ischemia. However, the long-term results of CABG using saphenous vein (SV) graft, compared to internal mammary artery (IMA) graft, have not been satisfactory. The SV graft failure is due to development of intimal hyperplasia, a process characterized by abnormal migration and proliferation of smooth muscle cells (SMCs) in the intimal layer of the vein graft. Insulin growth factor 1 (IGF-1) is a major mitogenic growth factor released at the site of the shear stress-induced graft injury. This study, for the first time, compares the extent of IGF-1-PI3K-Akt activation in isolated human by pass graft conduits. Human SV and IMA vessels were collected and SMCs isolated and cultured. In cultured SMCs, effect of IGF-1 was examined on total and phosphorylated PI3K, Akt and IGF-1R by Western blot analysis. Cell proliferation was measured using BrdU ELISA. There was no significant difference in the basal expression of phosphorylated PI3K, Akt and IGF-1R in SV and IMA SMCs from human bypass conduits. However, we observed an upregulation of IGF-1 receptors in the SV SMCs in response to IGF-1 stimulation with no effect in IMA SMCs. Furthermore, the immunoblotting and cellular activation of signaling ELISA (CASE) assay demonstrated a significantly higher activity of both PI3K and Akt in IGF-1-stimulated SV SMCs than IMA. This was inhibited by an IGF-1R blocking antibody. IGF-1 induced proliferation in both SV and IMA SMCs was inhibited by a PI3K inhibitor, wortmannin. These data demonstrate differential activity of IGF-1-induced PI3K-Akt activation, which was quantitatively and temporally greater in SV SMCs than in the IMA. This, at least in part, could explain the greater propensity of the SV conduits than the IMA to undergo intimal hyperplasia following CABG.
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影响因子：
20.1
作者：
Radcliff, K;Tang, TB;Tintut, Y
通讯作者：
Tintut, Y
影响因子：
3.5
作者：
Chisalita, S. I.;Johansson, G. S.;Arnqvist, H. J.
通讯作者：
Arnqvist, H. J.
影响因子：
1.7
作者：
Myit, S;Delafontaine, P;Brink, M
通讯作者：
Brink, M
DOI：
10.1016/j.bbrc.2010.03.072
发表时间：
2010-04-09
影响因子：
3.1
作者：
Furundzija, Vesna;Fritzsche, Jan;Stawowy, Philipp
通讯作者：
Stawowy, Philipp
影响因子：
5.3
作者：
Mitra AK;Jia G;Gangahar DM;Agrawal DK
通讯作者：
Agrawal DK