Induction of connective tissue growth factor (CTGF) in human endothelial cells by lysophosphatidic acid, sphingosine-1-phosphate, and platelets
Induction of connective tissue growth factor (CTGF) in human endothelial cells by lysophosphatidic acid, sphingosine-1-phosphate, and platelets
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DOI：
10.1016/j.atherosclerosis.2004.04.011
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发表时间：
2004-08-01
期刊：
影响因子：
5.3
通讯作者：
Goppelt-Struebe, M
中科院分区：
文献类型：
--
作者：
Muehlich, S;Schneider, N;Goppelt-Struebe, M
内皮功能障碍的特征在于内皮细胞和血液成分之间的多种相互作用。本研究主要探讨生物活性脂质和血小板对内皮细胞中致动脉粥样硬化结缔组织生长因子（CTGF）的诱导作用。溶血磷脂酸（LPA）和鞘氨醇-1-磷酸（S1 P）导致CTGF mRNA和蛋白表达在人内皮细胞系EAHY 926和人脐静脉内皮细胞（HUVEC）的原代培养物中的时间和浓度依赖性增加。由于这两种细胞类型表达LPA和S1 P的各种受体，因此通过药理学手段进一步表征了信号传导途径：CTGF的诱导对百日咳毒素不敏感，并且抑制p42/44 MAP激酶的活化仅部分降低CTGF表达。相反的，我不知道。辛伐他汀、香叶基香叶基转移酶抑制剂或Rho激酶抑制剂Y27632对RhoA信号通路的干扰阻止了CTGF的诱导。血管内皮细胞与新鲜分离的人血小板共孵育可显著增加血管内皮细胞CTGF mRNA的表达，血管内皮细胞对辛伐他汀敏感，LPA、SIP或血小板诱导血管内皮细胞CTGF表达上调可能参与动脉粥样硬化的发生和发展。辛伐他汀干扰这种促动脉粥样硬化因子的合成进一步支持了他汀类药物的抗动脉粥样硬化作用。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Endothelial dysfunction is characterized by multiple interactions between endothelial cells and components of the blood. This study focussed on the induction of the pro-atherogenic connective tissue growth factor (CTGF) in endothelial cells by bioactive lipids and platelets. Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) led to a time- and concentration-dependent increase in CTGF mRNA and protein expression in the human endothelial cell line EAHY 926 and in primary cultures of human umbilical vein endothelial cells (HUVEC). As both cell types expressed various receptors for LPA and S1P, signaling pathways were further characterized by pharmacological means: induction of CTGF was pertussis toxin-insensitive and inhibition of activation of p42/44 MAP kinases only partially reduced CTGF expression. On the contrary. interference with the RhoA signaling pathway by simvastatin, an inhibitor of geranylgeranyltransferases, or the Rho-kinase inhibitor Y27632 prevented induction of CTGF. Co-incubation of endothelial cells with freshly isolated human platelets significantly increased the expression of CTGF mRNA in endothelial cells, which was also sensitive to simvastatin.Up-regulation of CTGF in endothelial cells, induced by LPA, SIP, or platelets, may contribute to the initiation and progression of atherosclerosis. Interference of simvastatin with the synthesis of this pro-atherogenic factor further supports the anti-atherogenic role of statins. (C) 2004 Elsevier Ireland Ltd. All rights reserved.