PDF(Sci-hub)
Abstract：
Long-term therapy with older antiepileptic drugs (AEDs), but not levetiracetam (LEV), may increase the risk of atherosclerosis (AS), suggesting that LEV may have a potential anti-AS effect. The synaptic vesicle 2A (SV2A) is known to the specific binding site of LEV. Numerous studies have documented that SV2A is a membrane protein specifically expressed in nervous system. Interestingly, our previous research showed that SV2A also existed in human CD8+ T lymphocytes. Therefore, we hypothesized that LEV was associated with decreased risk of AS by regulating monocytes chemotaxis and adhesion. We showed that SV2A protein were detected in THP-1 human monocytic leukemia cells. LEV (300 μM) inhibited the chemotaxis and adhesion of THP-1 cells after transfection with plasmids expressing SV2AWT, but not SV2AR383Q which was a known functional mutation site of human SV2A. Furthermore, RT-PCR and western blot analysis demonstrated that LEV (300 μM) decreased the expression level of chemokine-related receptors (CX3CL1, CCR1, CCR2, and CCR5),and reduced levels of phosphorylated AKT (p-AKT) in THP-1 cells with SV2AWT expressing plasmids. Taken together, these findings indicated that LEV has an inhibitory effect on THP-1 monocyte adhesion and chemotaxis, suggesting that SV2A may serve as a novel therapeutic target to prevent AS.
摘要：
使用老年抗癫痫药物（AEDs）的长期治疗，但不是左乙拉西坦（LEV），可能会增加动脉粥样硬化（AS）的风险，提示LEV可能具有潜在的抗AS作用。已知突触小泡2A(SV2A)是LEV的特异性结合位点。大量研究表明，SV2A是一种在神经系统中特异性表达的膜蛋白。有趣的是,我们之前的研究表明SV2A也存在于人类CD8+T淋巴细胞中。因此,我们假设LEV通过调节单核细胞趋化和粘附而降低AS风险.我们显示在THP-1人单核细胞白血病细胞中检测到SV2A蛋白。LEV（300μM）抑制表达SV2AWT的质粒转染后THP-1细胞的趋化和粘附，但不是SV2AR383Q，这是人类SV2A的已知功能突变位点。此外，RT-PCR和westernblot分析表明，LEV（300μM）降低趋化因子相关受体（CX3CL1，CCR1，CCR2和CCR5）的表达水平，用SV2AWT表达质粒降低THP-1细胞中磷酸化AKT(p-AKT)的水平。一起来看,这些发现表明LEV对THP-1单核细胞粘附和趋化具有抑制作用，提示SV2A可能成为预防AS的新治疗靶点。
