Inhibitory effect of fenofibrate on neointima hyperplasia via G0/G1 arrest of cell proliferation
Inhibitory effect of fenofibrate on neointima hyperplasia via G0/G1 arrest of cell proliferation
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DOI：
10.1016/j.ejphar.2010.10.046
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发表时间：
2011-01-10
影响因子：
5
通讯作者：
Yun, Yeo-Pyo
中科院分区：
文献类型：
--
作者：
Lee, Jung-Jin;Yu, Ji-Yeon;Yun, Yeo-Pyo
本研究采用雄性SD大鼠球囊扩张血管损伤模型，观察非诺贝特对血管内膜增生的影响，并采用原代培养的大鼠主动脉平滑肌细胞（SMC），观察其增殖情况，以探讨非诺贝特对血管内膜增生的影响及其可能的分子机制。非诺贝特治疗组的新生内膜形成显著减少，距对照（0 07 +/- 004 m（2））（013 ± 004 mm（2））非诺贝特显著抑制血小板源性生长因子（PDGF）-BB诱导的细胞计数，[H-3]-胸苷掺入DNA非诺贝特抑制PDGF-BB诱导的G（0）/G（1）进程此外，非诺贝特不仅抑制视网膜母细胞瘤（Rb）蛋白磷酸化和细胞周期蛋白D/E、CDK 2/4和增殖细胞核抗原（PCNA）蛋白的表达，而且还抑制丝裂原活化蛋白激酶（MAPK）信号通路如ERK 1/ERK 2/ERK 3/ERK 2/MAPK 2/3 MAPK 2/2 p38和JNK磷酸化总之，本研究表明非诺贝特通过G（0）/G（1）显著抑制新生内膜形成，抑制PDGF BB诱导的细胞增殖与抑制MAPK相关，导致细胞周期蛋白D/E CDK 2/4和PCNA蛋白表达下调，表明非诺贝特可能对血栓形成或心血管疾病高风险个体有用（C）2010 Elsevier B V保留所有权利
We have previously reported that fenofibrate displayed a potent antithrombotic effect by the inhibition of platelet aggregation The present study was designed to investigate the effects of fenofibrate on the neointimal hyperplasia and Its possible molecular mechanism Neointimal hyperplasia was measured in balloon inflated-induced vascular injury model of male Sprague-Dawley rats and cell proliferation was measured in primary cultured rat aortic vascular smooth muscle cells (VSMCs) Fenofibrate-treated group showed a significant reduction in neointimal formation (0 07 +/- 004 m(2)) from the control (0 13 +/- 0 04 mm(2)) Fenofibrate significantly inhibited platelet-derived growth factor (PDGF)-BB-induced cell counting and [H-3]-thymidine incorporation into DNA Fenofibrate suppressed the PDGF BB-inducible progression through G(0)/G(1) to S phase of cell cycle Moreover fenofibrate inhibited not only phosphorylation of retinoblastoma (Rb) protein and expression of cyclin D/E CDK 2/4 and proliferating cell nuclear antigen (PCNA) proteins but also mitogen activated protein kinase (MAPK) signaling pathways such as ERK 1/2 p38 and JNK phosphorylation In conclusion the present study demonstrates that fenofibrate significantly inhibits neointimal formation via G(0)/G(1), arrest of PDGF BB induced cell proliferation in association with the inhibition of MAPK which resulted in the downregulation of expressions of cyclin D/E CDK 2/4 and PCNA proteins suggesting that fenofibrate may be useful for individuals with a high risk of thrombotic or cardiovascular diseases (C) 2010 Elsevier B V All rights reserved