Innate immunity has a dual effect on vascular healing: Suppression and aggravation of neointimal formation and remodeling post-endotoxin challenge
Innate immunity has a dual effect on vascular healing: Suppression and aggravation of neointimal formation and remodeling post-endotoxin challenge
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DOI：
10.1016/j.atherosclerosis.2007.10.034
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发表时间：
2008-07-01
期刊：
影响因子：
5.3
通讯作者：
Danenberg, H. D.
中科院分区：
文献类型：
--
作者：
Epstein, H.;Grad, E.;Danenberg, H. D.
背景：炎症对损伤后的血管修复、调节新生内膜增殖和重塑非常重要。以前，我们已经证明低强度的炎症反应加速了球囊和支架损伤后的新生内膜形成。本研究检查了非特异性炎症的程度和时间的调节是否以单向或双向的方式介导局部血管反应。方法和结果：兔髂动脉剥脱和球囊损伤后，用低浓度的（1 μ g/kg）或高剂量（100 μ g/kg）的细菌内毒素（LPS），或在损伤前3天给予早期高剂量LPS（预处理）。与对照组（0.3 +/- 0.03 mm 2）相比，低剂量组（0.537 +/- 0.059 mm 2）28天时的新生内膜形成显著增加。高剂量LPS没有显著影响新生内膜形成，而早期高剂量显著减少新生内膜（分别为0.296 +/- 0.033和0.194 +/- 0.025 mm（2），n = 12-14/组）。动脉壁和全身循环白细胞介素-1 β水平和单核细胞CD 14活化与新生内膜形成相关。低剂量或高剂量LPS处理的动物血管重塑加速，而预处理组不受影响。重塑指数与动脉基质金属蛋白酶-2水平呈负相关6 days after injurie.Conclusions：非特异性炎症的程度和时间，同时与血管损伤，可以确定不同的和相反的血管修复模式。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
Background: Inflammation is important to vascular repair following injury, modulating neointimal proliferation and remodeling. Previously, we have shown that a low-intensity inflammatory response aggravates neointimal formation following balloon and stent injury. The present study examined whether modulation of the extent and timing of nonspecific inflammation mediates the local vascular response in an additive unidirectional or rather a bidirectional fashion.Methods and results: Rabbits subjected to denudation and balloon injury of the iliac artery were treated with low (1 mu g/kg) or high (100 mu g/kg) doses of bacterial endotoxin (LPS) immediately after injury, or with early high-dose LPS administered 3 days prior to injury (preconditioning). Neointimal formation at 28 days was significantly increased in the low-dose group (0.537 +/- 0.059 mm 2) as compared with controls (0.3 +/- 0.03 mm(2)). High-dose LPS did not significantly affect neointimal formation while early high dose significantly reduced neointima (0.296 +/- 0.033 and 0.194 +/- 0.025 mm(2), respectively, n = 12-14/group). Arterial wall and systemically circulating interleukin-1 beta levels, and monocyte CD14 activation correlated with neointimal formation. Vascular remodeling was accelerated in animals treated with low- or high-dose LPS while not affected in the preconditioned group. Remodeling index inversely correlated with arterial matrix metalloproteinase-2 levels 6 days after injury.Conclusions: The extent and timing of nonspecific inflammation that is concurrent with vascular injury can determine different and opposite vascular repair patterns. (C) 2007 Elsevier Ireland Ltd. All rights reserved.