Reconstituted HDL containing human apolipoprotein A-1 reduces VCAM-1 expression and neointima formation following periadventitial cuff-induced carotid injury in apoE null mice
Reconstituted HDL containing human apolipoprotein A-1 reduces VCAM-1 expression and neointima formation following periadventitial cuff-induced carotid injury in apoE null mice
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DOI：
10.1006/bbrc.1999.1278
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发表时间：
1999-10-22
影响因子：
3.1
通讯作者：
Cercek, B
中科院分区：
文献类型：
--
作者：
Dimayuga, P;Zhu, J;Cercek, B
动脉损伤触发炎症反应，部分由诱导粘附分子如血管细胞粘附分子-1（VCAM-1）介导，并与新生内膜增厚有关。由于已知HDL可降低精氨酸激活的VCAM-1表达，我们测试了含有血浆来源的apoA-1（rHDL）的重组人HDL抑制动脉损伤后VCAM-1表达和血管壁增厚的假设。小鼠每隔一天静脉内接受rHDL（40 mg/kg），持续3周。与对照组相比，rHDL治疗组在损伤后21天抑制了新生内膜形成（0.008 +/- 0.004 mm（2）vs. 0.037 +/- 0.019 mm（2）; P < 0.01），减少了VCAM-1表达，并在损伤后第一周内通过组织形态计量学分析减少了单核细胞/巨噬细胞浸润。这些变化对血浆总胆固醇和HDL胆固醇水平以及动脉组织胆固醇水平没有任何影响。在损伤后的第一周内，与对照相比，rHDL处理还减少了动脉壁中修饰的脂蛋白的形成。该发现表明rHDL的抗氧化作用与动脉损伤后VCAM-1表达和新生内膜形成的减少相关，（C）1999 Academic Press。
Arterial injury triggers an inflammatory response in part mediated by induction of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and is implicated in neointimal thickening. Since HDL is known to reduce cytokine-activated VCAM-1 expression, we tested the hypothesis that VCAM-1 expression and neontimal thickening following arterial injury are inhibited by reconstituted human HDL containing plasma-derived apoA-1 (rHDL), We used the carotid cuff injury in apoE (-/-) mice fed high cholesterol. Mice received rHDL (40 mg/kg) intravenously every other day for 3 weeks. Compared to control, rHDL treatment inhibited neointima formation (0.008 +/- 0.004 mm(2) vs. 0.037 +/- 0.019 mm(2); P < 0.01) 21 days after injury, reduced VCAM-1 expression, and decreased monocyte/macrophage infiltration as assessed by histomorphometric analysis within the first week after injury. These changes occurred without any effect on plasma total and HDL cholesterol levels as well as the arterial tissue cholesterol levels. rHDL treatment also reduced the formation of modified lipoprotein in the arterial wall compared to control within the first week after injury, This finding suggests an antioxidant effect of rHDL associated with reduced VCAM-1 expression and neointimal formation after arterial injury, (C) 1999 Academic Press.