Department of Vascular Surgery, University of Heidelberg, D-69120 Heidelberg, Germany.
Int J Mol Med. 2013 Aug;32(2):331-8. doi: 10.3892/ijmm.2013.1401. Epub 2013 May 30.
The aim of this study was to evaluate in detail the histopathological characteristics of endarterectomized carotid atherosclerotic lesions in symptomatic versus asymptomatic patients. Twenty carotid lesions, 10 from asymptomatic and 10 from symptomatic patients who underwent carotid endarterectomy were classified according to histomorphological features. Samples were analyzed for intraplaque localization and for the expression of proteins associated with inflammation, such as CD68, interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), pentraxin-3 (PTX-3), nuclear factor-κB (NF-κB), C-reactive protein (CRP) and transforming growth factor-β (TGF-β), as well as for proteins associated with vascular remodelling, such as matrix-metalloproteinase-9 (MMP-9), glycophorin A (GYPA), osteoprotegerin (OPG), vascular cell adhesion molecule-1 (VCAM-1), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF) and vascular smooth muscle cell actin (VSMA). Corresponding expression scores were compared between the symptomatic and asymptomatic patients and evaluated statistically. The expression of all 14 evaluated markers was significantly elevated in the border zone adjacent to the mixed plaque compared with the unaffected control area of the same sample (p<0,016). The expression scores of GYPA and OPG were significantly higher in the border zones around the calcified (GYPA, p=0.035; OPG, p=0.043) and mixed (GYPA, p<0.001; OPG, p=0.007) plaque zones of symptomatic patients compared to asymptomatic patients. No difference in expression scores was observed for any of the analyzed inflammatory marker proteins between the border zones of symptomatic and asymptomatic patients. In conclusion, the increased expression of GYPA, indicating intraplaque hemorrhage, and OPG, indicating the transdifferentiation of vascular cells, in carotid atherosclerotic lesions may be associated with an increased risk of plaque instability.
本研究旨在详细评估症状性与无症状性颈动脉粥样硬化病变患者颈动脉内膜切除术后的组织病理学特征。根据组织形态学特征,将 20 例颈动脉病变(10 例来自无症状患者,10 例来自有症状患者)分为几类。对斑块内的定位以及与炎症相关的蛋白(如 CD68、白细胞介素(IL)-1β、肿瘤坏死因子-α(TNF-α)、五聚素-3(PTX-3)、核因子-κB(NF-κB)、C 反应蛋白(CRP)和转化生长因子-β(TGF-β))以及与血管重塑相关的蛋白(如基质金属蛋白酶-9(MMP-9)、糖蛋白 A(GYPA)、护骨素(OPG)、血管细胞黏附分子-1(VCAM-1)、内皮素-1(ET-1)、血管内皮生长因子(VEGF)和血管平滑肌肌动蛋白(VSMA))的表达进行分析。比较了症状性和无症状性患者之间的相应表达评分,并进行了统计学评估。与同一样本中未受影响的对照区域相比,混合斑块相邻的边界区域中所有 14 种评估标志物的表达均显著升高(p<0.016)。与无症状患者相比,在有症状患者的钙化(GYPA,p=0.035;OPG,p=0.043)和混合(GYPA,p<0.001;OPG,p=0.007)斑块区域周围的边界区域中,GYPA 和 OPG 的表达评分明显更高。在症状性和无症状性患者的边界区域之间,没有观察到任何分析的炎症标志物蛋白的表达评分存在差异。总之,GYPA 表达增加表明斑块内出血,OPG 表达增加表明血管细胞的转分化,这可能与斑块不稳定的风险增加有关。