Accelerated intimal thickening in carotid arteries of balloon-injured rats after immunization against heat shock protein 70
Accelerated intimal thickening in carotid arteries of balloon-injured rats after immunization against heat shock protein 70
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DOI：
10.1016/s0735-1097(01)01579-0
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发表时间：
2001-11-01
影响因子：
24
通讯作者：
Keren, G
中科院分区：
文献类型：
--
作者：
George, J;Greenberg, S;Keren, G
本研究的目的是验证热休克蛋白（Hsp） 70的免疫反应诱导会增加大鼠颈动脉损伤模型的内膜增厚的假设。背景：由内膜增厚引起的再狭窄是冠状动脉成形术长期成功的主要限制因素。一些研究表明，感染因子会增加再狭窄。热休克蛋白是高度保守的结构，由所有细胞在非特异性应激形式下产生。已知感染因子含有Hsp70，它具有明显的免疫原性，可引起强烈的免疫反应。方法采用Hsp70免疫（n = 11）、牛血清白蛋白（[BSA] n = 9）和对照佐剂（n = 10）分别免疫大鼠，研究Hsp70免疫是否影响新生内膜增厚。三周后，使用相同的方案增强大鼠，以实现对Hsp70的持续免疫反应，之后对所有动物进行颈动脉损伤。结果Western blotting和免疫组化结果显示，动脉损伤与损伤诱导后3、7、14天Hsp70表达上调有关。与BSA或对照组相比，hsp70免疫大鼠的内膜面积和内膜/内侧比值显著增加。结论：球囊损伤动脉中Hsp70的上调可作为抗Hsp70免疫反应的靶点，从而促进内膜增厚。这些观察结果可能提供了一种可能的机制来解释与感染性病原体发生有关的内膜增厚加速。[J]中华医学会心脏科杂志，2001;38(1):1 - 4。
OBJECTIVES The goal of this study was to test the hypothesis that induction of an immune response to heat shock protein (Hsp) 70 would increase intimal thickening in a rat carotid-injury model.BACKGROUND Restenosis resulting from intimal thickening poses a major limitation to the long-term success of coronary angioplasty. Several studies have proposed that infectious agents increase restenosis. Heat shock proteins are highly conserved structures, produced by all cells in response to nonspecific forms of stress. Infectious agents are known to contain Hsp70, which is markedly immunogenic and can elicit a strong immune response.METHODS To investigate whether Hsp70 immunity can affect neointimal thickening, we immunized rats with either Hsp70 (n = 11), bovine serum albumin ([BSA] n = 9) or with a control adjuvant (n = 10). Three weeks later, rats were boosted using the same regimen to achieve a sustained immune response to Hsp70 after which carotid injury was applied to all animals.RESULTS Arterial injury was associated with upregulation of Hsp70, 3, 7 and 14 days after induction of the injury as evidenced by Western blotting and immunohistochemistry. Intimal area and intimal/medial ratio was significantly increased in Hsp70-immunized rats in comparison with BSA or control-injected rats.CONCLUSIONS Our results imply that upregulation of Hsp70 in balloon-injured arteries can serve as a target for anti-Hsp70 immune response, thereby facilitating enhanced intimal thickening. These observations may provide a possible mechanism that explains the accelerated intimal thickening that has been associated with the occurrence of infectious pathogens. (J Am Coll Cardiol 2001;38:1564-9) (C) 2001 by the American College of Cardiology.