Differential effects of chlorinated and oxidized phospholipids in vascular tissue: implications for neointima formation
Differential effects of chlorinated and oxidized phospholipids in vascular tissue: implications for neointima formation
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DOI：
10.1042/cs20140578
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发表时间：
2015-05-01
期刊：
影响因子：
6
通讯作者：
Kennedy, Simon
中科院分区：
文献类型：
--
作者：
Greig, Fiona H.;Hutchison, Lisa;Kennedy, Simon
血管损伤后动脉壁炎症细胞和MPO（髓过氧化物酶）的存在可通过磷脂修饰促进新内膜的形成。本研究探讨了这些磷脂，特别是氧化和氯化的磷脂，如何在受损血管内发生改变，以及它们如何影响血管平滑肌细胞的重塑过程。采用左颈动脉（LCA）钢丝剥脱结扎法诱导C57BL/6小鼠和高脂喂养ApoE（-/-）小鼠血管损伤。使用免疫组织化学和ESI-MS评估内膜和内侧成分。我们利用兔主动脉平滑肌细胞（SMCs）在细胞水平上研究了修饰脂质对VSMC增殖、活力和迁移的影响。以内膜/中膜比测量，ApoE（-/-）线损伤小鼠的内膜面积显著增大（3.62 +/- 0.49，而C57BL/6小鼠为0.83 +/- 0.25,n=3），氧化低密度脂蛋白（oxLDL）浸润增加，血浆MPO水平升高。在导线损伤的ApoE（-/-）颈动脉中，溶血磷脂酰胆碱和不饱和磷脂酰胆碱（PCs）也相对增加。氯化脂类对VSMC的增殖、活力或迁移没有影响，而氧化磷脂的慢性孵育在胎牛血清的存在下刺激了增殖[与对照组相比，1 μ M PGPC（1-棕榈酰-2-戊二酰- n-甘油-3-磷酸胆碱）的活细胞为154.8 +/- 14.2%,n=6]。总之，具有炎症表型的ApoE（-/-）小鼠在电线损伤的动脉中产生更多的新内膜，而血管壁中氧化脂质的积累可能会传播这种效应。
The presence of inflammatory cells and MPO (myeloperoxidase) in the arterial wall after vascular injury could increase neointima formation by modification of phospholipids. The present study investigates how these phospholipids, in particular oxidized and chlorinated species, are altered within injured vessels and how they affect VSMC (vascular smooth muscle cell) remodelling processes. Vascular injury was induced in C57BL/6 mice and high fat-fed ApoE(-/-) (apolipoprotein E) mice by wire denudation and ligation of the left carotid artery (LCA). Neointimal and medial composition was assessed using immunohistochemistry and ESI-MS. Primary rabbit aortic SMCs (smooth muscle cells) were utilized to examine the effects of modified lipids on VSMC proliferation, viability and migration at a cellular level. Neointimal area, measured as intima-to-media ratio, was significantly larger in wire-injured ApoE(-/-) mice (3.62 +/- 0.49 compared with 0.83 +/- 0.25 in C57BL/6 mice, n=3) and there was increased oxidized low-density lipoprotein (oxLDL) infiltration and elevated plasma MPO levels. Relative increases in lysophosphatidylcholines and unsaturated phosphatidylcholines (PCs) were also observed in wire-injured ApoE(-/-) carotid arteries. Chlorinated lipids had no effect on VSMC proliferation, viability or migration whereas chronic incubation with oxidized phospholipids stimulated proliferation in the presence of fetal calf serum [154.8 +/- 14.2% of viable cells at 1 mu M PGPC (1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine) compared with control, n=6]. In conclusion, ApoE(-/-) mice with an inflammatory phenotype develop more neointima in wire-injured arteries and accumulation of oxidized lipids in the vessel wall may propagate this effect.