Department of Internal Medicine, Wuppertal Research and Medical Center, Angiology Wuppertal, Germany.
Eur Rev Med Pharmacol Sci. 2013 Nov;17(21):2874-83.
Statins are HMG-CoA reductase inhibitors within the framework of cholesterol biosynthesis and used to lower the low-density lipoprotein (LDL). There are other aspects of statins can deploy a protective effect, even without the LDL's lowering. The aim of this study is to investigate the effects of different type of statins on proliferative and migrative behaviors of Hepatocyte Growth Factor (HGF) induced human umbilical vein endothelial cells (HUVECs).
Human umbilical vein endothelial cells were isolated and cultured. Groups were designed in order to observe the effects of every individual substance. HUVECs were stimulated with HGF, statins and farnesylpyrophosphat ammonium salt (FPP) or geranylgeranyl-pyrophosphate (GGPP), respectively. Cell proliferations were counted 48 hours after initial stimuli and distances between migration fronts were used in migration analyses.
All types of statins showed significant anti-migrative and anti-proliferative characters. Simvastatin and fluvastatin but not cerivastatin, were able to inhibit the HGF-depending migration and showed a significant effect on the inhibition of the isoprenylation (GGPP). Only simvastatin influenced the HGF-depending migration via inhibiting the isoprenylation process through GGPP. Cerivastatin significantly decreased the proliferation and Fluvastatin significantly enhanced the migration behaviors of HUVECs when they were co-incubated with methyl-8-cyclodextrin (MCD).
Statins countermand the proproliferative and as well as the promigrative effect of HGF on HUVECs. The mechanisms which provoke this effect are dependent on the type of statin. Direct interactions of statins with lipid rafts play a significant role in the endothelial cell mechanisms.
他汀类药物是胆固醇生物合成框架内的 HMG-CoA 还原酶抑制剂，用于降低低密度脂蛋白（LDL）。他汀类药物还有其他方面可以发挥保护作用，甚至在不降低 LDL 的情况下也是如此。本研究旨在探讨不同类型的他汀类药物对肝细胞生长因子（HGF）诱导的人脐静脉内皮细胞（HUVEC）增殖和迁移行为的影响。
分离并培养人脐静脉内皮细胞。设计了不同的组来观察每种物质的作用。用 HGF、他汀类药物和法呢基焦磷酸铵盐（FPP）或香叶基焦磷酸（GGPP）分别刺激 HUVEC。初始刺激后 48 小时计数细胞增殖，使用迁移前沿之间的距离进行迁移分析。
所有类型的他汀类药物均表现出显著的抗迁移和抗增殖特性。辛伐他汀和氟伐他汀，但不是西立伐他汀，能够抑制 HGF 依赖性迁移，并对异戊烯基化（GGPP）有显著影响。只有辛伐他汀通过抑制 GGPP 抑制异戊烯基化过程来影响 HGF 依赖性迁移。西立伐他汀显著降低了增殖，氟伐他汀在与甲基-β-环糊精（MCD）共孵育时显著增强了 HUVEC 的迁移行为。
他汀类药物抵消了 HGF 对 HUVEC 的促增殖和促迁移作用。引起这种作用的机制取决于他汀类药物的类型。他汀类药物与脂筏的直接相互作用在血管内皮细胞机制中起着重要作用。
