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首页> 外文期刊>Life sciences >Sphingomyelin synthase 2 over-expression induces expression of aortic inflammatory biomarkers and decreases circulating EPCs in ApoE KO mice
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Sphingomyelin synthase 2 over-expression induces expression of aortic inflammatory biomarkers and decreases circulating EPCs in ApoE KO mice

机译：鞘磷脂合成酶2的过表达诱导ApoE KO小鼠主动脉炎性生物标志物的表达并减少循环EPC

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Aims: This study sought to assess the effect of sphingomyelin synthase 2 (SMS2) over-expression on plaque component and endothelial dysfunction in atherosclerosis. Main methods: We generated recombinant adenovirus vectors containing human SMS2 cDNA (AdV-SMS2) or control gene GFP cDNA (AdV-GFP). Both AdVs were injected (i.v.) into ApoE KO mice to establish SMS2 over-expressing and control mice models, respectively. The mice were fed a high fat diet for 30 days. We then examined their plasma lipid levels, expression levels of aortic inflammatory biomarkers critical for the plaque's stability, and numbers of peripheral endothelial progenitor cells (EPC). Key findings: Compared with the control mice, SMS2 over-expression had significantly (1) increased aortic matrix metalloproteinase-2 (MMP-2), monocyte chemoattractant protein-1 (MCP-1), tissue factor (TF) and cyclooxygenase-2 (COX-2) mRNA levels (1.9-fold, 2.2-fold, 2.6-fold and 3.2-fold, respectively, P < 0.01) and protein levels (2.2-fold, 1.9-fold, 1.9-fold and 2.1-fold, respectively, P < 0.01); (2) increased MMP-2, COX-2 in situ expression in aortic root (2.6-fold and 2.3-fold, respectively, P < 0.01); (3) decreased aortic COX-1 mRNA levels (65%, P < 0.01) and protein levels (64%, P < 0.01); and (4) decreased CD34/KDR-positive cells (33%, P < 0.01), circulating angiogenic cells (CACs) (50%, P < 0.05), and colony forming units (CFUs) (40%, P < 0.05) in circulation. Significance: SMS2 over-expression was probably associated with increased expression of aortic inflammatory biomarkers, as well as decreased numbers of CD34/KDR-positive cells, CACs and CFUs in circulation. Therefore, SMS2 over-expression might correlate with endothelial dysfunction and aggravate atherosclerotic plaque instability in ApoE KO mice.
机译：目的：本研究旨在评估鞘磷脂合酶2（SMS2）的过表达对动脉粥样硬化斑块成分和内皮功能障碍的影响。主要方法：我们产生了包含人SMS2 cDNA（AdV-SMS2）或对照基因GFP cDNA（AdV-GFP）的重组腺病毒载体。将两种AdV都注射（静脉内）到ApoE KO小鼠中以分别建立SMS2过表达和对照小鼠模型。给小鼠喂高脂饮食30天。然后，我们检查了它们的血浆脂质水平，对斑块稳定性至关重要的主动脉炎性生物标志物的表达水平以及外周内皮祖细胞（EPC）的数量。主要发现：与对照组小鼠相比，SMS2的过表达显着（1）主动脉基质金属蛋白酶2（MMP-2），单核细胞趋化蛋白1（MCP-1），组织因子（TF）和环氧合酶2增加（COX-2）mRNA水平（分别为1.9倍，2.2倍，2.6倍和3.2倍，P <0.01）和蛋白质水平（2.2倍，1.9倍，1.9倍和2.1倍，分别为P <0.01）; （2）主动脉根中MMP-2，COX-2的原位表达增加（分别为2.6倍和2.3倍，P <0.01）; （3）主动脉COX-1 mRNA水平（65％，P <0.01）和蛋白质水平（64％，P <0.01）降低; （4）CD34 / KDR阳性细胞减少（33％，P <0.01），循环血管生成细胞（CAC）（50％，P <0.05）和菌落形成单位（CFU）（40％，P <0.05）流通中。意义：SMS2的过表达可能与主动脉炎性生物标志物的表达增加以及循环中CD34 / KDR阳性细胞，CAC和CFU的数量减少有关。因此，SMS2过表达可能与ApoE KO小鼠的内皮功能障碍和加重动脉粥样硬化斑块的不稳定性有关。

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