Lovastatin exerts protective effects on endothelial cells via upregulation of PTK2B.
Lovastatin exerts protective effects on endothelial cells via upregulation of PTK2B.
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DOI：
10.3892/etm.2016.3547
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发表时间：
2016-09
影响因子：
2.7
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Chu W;Guan L;Huang D;Ren Y;Zhou Y
他汀类药物是HMG-CoA还原酶抑制剂，用于降低低密度脂蛋白（LDL）的血液水平。此外，已证明它们在不存在LDL降低活性的情况下发挥多效性保护作用。本研究探讨洛伐他汀对人脐静脉内皮细胞（HUVECs）基因表达的影响，以进一步探讨其对氧化型低密度脂蛋白（ox-LDL）诱导的细胞毒性的保护作用。用洛伐他汀处理HUVECs 2-24 h，并使用cDNA微阵列分析基因表达模式。结果表明，洛伐他汀调控了许多基因，包括与细胞存活相关的某些基因，如PTK 2B，BCL 2和MAP 3 K3。特别是，PTK 2B，这已被证明发挥抗氧化低密度脂蛋白诱导的细胞损伤的抗凋亡作用，上调洛伐他汀。PTK 2B的敲低能够减轻ox-LDL诱导的细胞损伤，这与磷酸化AKT和eNOS水平降低以及细胞依赖性凋亡的抑制有关。总之，本研究的结果表明，洛伐他汀保护氧化低密度脂蛋白诱导的细胞损伤，可能通过上调PTK 2B，调节抗凋亡信号通路。
Statins are HMG-CoA reductase inhibitors that are used to decrease the blood levels of low-density lipoprotein (LDL). In addition, they have been shown to exert pleiotropic protective effects in the absence of LDL-lowering activity. The present study investigated the effects of lovastatin on global gene expression in human umbilical vein endothelial cells (HUVECs), in order to further explore its ability to protect against oxidized (ox)-LDL-induced cytotoxicity. HUVECs were treated with lovastatin for 2–24 h, and gene expression patterns were analyzed using cDNA microarrays. The results suggested that numerous genes were regulated by lovastatin, including certain genes associated with cell survival, such as PTK2B, BCL2 and MAP3K3. In particular, PTK2B, which has been shown to exert anti-apoptotic effects against ox-LDL-induced cell injury, was upregulated by lovastatin. Knockdown of PTK2B was able to attenuate ox-LDL-induced cell injury, and this was associated with decreased levels of phosphorylated-AKT and eNOS, and inhibition of mitochondrial-dependent apoptosis. In conclusion, the results of the present study suggested that lovastatin protects against ox-LDL-induced cell injury, potentially via the upregulation of PTK2B, which regulates the anti-apoptosis signaling pathway.