Increased expression of inhibitor of apoptosis proteins in atherosclerotic plaques of symptomatic patients with carotid stenosis
Increased expression of inhibitor of apoptosis proteins in atherosclerotic plaques of symptomatic patients with carotid stenosis
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DOI：
10.1016/j.yexmp.2006.09.006
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发表时间：
2007-08-01
影响因子：
3.6
通讯作者：
Agrawal, Devendra K.
中科院分区：
文献类型：
--
作者：
Moran, Edward P.;Agrawal, Devendra K.
血管重塑和动脉粥样硬化病变的形成部分取决于血管平滑肌细胞（VSMCs）的凋亡和存活之间的平衡。在慢性阶段，动脉粥样硬化斑块中的VSMC的凋亡有助于斑块的弱化和潜在破裂，从而引起诸如急性冠状动脉综合征的病理。有症状患者斑块中的细胞凋亡发生率高于无症状患者，但存活蛋白（包括凋亡抑制蛋白（IAP））的表达尚未得到彻底研究。本研究的目的是探讨细胞凋亡抑制蛋白-2（cIAP 2），X连锁凋亡抑制蛋白（XIAP）和生存素在正常颈动脉，颈动脉内膜切除术标本的症状和无症状的颈动脉狭窄患者的免疫组化表达。结果显示，无症状斑块中平滑肌肌球蛋白重链抗原（SM-MHC）（sm 2）、增殖细胞核抗原（PCNA）和NF-κ β p50亚单位的免疫阳性率高于有症状斑块。此外，有症状的斑块中cIAP 2、XIAP和生存素的表达高于无症状斑块，这抑制了caspase-3的表达。有症状斑块中IAP表达增加可能是由于内源性防御机制，以防止斑块中释放的炎症刺激物的促凋亡作用。这可能与症状性动脉粥样硬化斑块的稳定有关，并可能成为潜在的治疗靶点。(c)2006年爱思唯尔公司All rights reserved.
Vascular remodeling and atheromatous lesion formation are determined in part by the balance between apoptosis and survival of vascular smooth muscle cells (VSMCs). In the chronic stages, apoptosis of VSMCs in the atherosclerotic plaques contributes to the weakening and potential rupture of the plaque causing pathologies such as acute coronary syndrome. The higher incidence of apoptosis in the plaques of symptomatic than in asymptomatic patients has been demonstrated, but the expression of survival proteins, including the inhibitor of apoptosis proteins (IAPs), has not been thoroughly examined. The aim of this study was to investigate the immunohistochemical expression of cellular inhibitor of apoptosis protein-2 (cIAP2), x-linked inhibitor of apoptosis protein (XIAP), and survivin in normal carotid arteries, and carotid endarterectomy specimens of symptomatic and asymptomatic patients with carotid stenosis. The results demonstrated stronger immunopositivity to smooth muscle myosin heavy chain antigen (SM-MHC) (sm2), proliferating cell nuclear antigen (PCNA), and p50 subunit of NF-kappa beta in the asymptomatic plaques than in symptomatic plaques. Furthermore, there was higher expression of cIAP2, XIAP, and survivin in the symptomatic than in the asymptomatic plaques and this paralleled caspase-3 expression. The increased expression of IAPs in symptomatic plaques could be due to endogenous defense mechanism to protect against the pro-apoptotic effect of the inflammatory stimuli that are released in the plaques. This could be involved in the stabilization of symptomatic atheromatous plaques and may prove a potential therapeutic target. (c) 2006 Elsevier Inc. All rights reserved.