Drożdż Katarzyna, Grzegorek Irmina, Chmielewska Magdalena, Gomułkiewicz Agnieszka, Jabłońska Karolina, Piotrowska Aleksandra, Karczewski Maciej, Janczak Dariusz, Patrzałek Dariusz, Dzięgiel Piotr, Szuba Andrzej
Regional Specialized Hospital in Wroclaw, Research and Development Center, Wroclaw, Poland; Department of Internal Medicine, 4th Military Hospital, Wroclaw, Poland.
APMIS. 2014 Sep;122(9):742-9. doi: 10.1111/apm.12212. Epub 2013 Dec 23.
Nogo-B (Reticulon 4B) is considered to be a novel vascular marker, which may have a protective role in injury-induced neointima formation and atherosclerosis. Nogo A/B is found to be crucial for monocyte/macrophage recruitment in acute inflammation and it is expressed in CD68 + macrophages. We hypothesize that macrophage infiltration in atherosclerosis is not dependent on Nogo-B expression in arterial wall. We have assessed Nogo-B expression and macrophage accumulation in the iliac arteries of healthy organ donors and organ donors with cardiovascular risk factors. Paraffin sections of 66 iliac arteries, from 44 deceased organ donors (17 women and 27 men), were studied. The healthy and cardiovascular risk (CVR) subgroups were created. With regard to staging of the atherosclerotic process, the thickness of arterial intima was measured in digitalized images of H+E stained tissue sections. Immunohistochemical reactions (Nogo-B and CD68) were carried out in all arteries (66 samples). Western blotting (WB-19 samples) and real-time PCR (27 samples) were performed on selected arteries. Significantly higher Nogo-B expression was demonstrated in the intima of the healthy subjects' subgroup, using immunohistochemistry. WB and real-time PCR revealed a trend toward lower Nogo-B expression in the adventitia of the CVR subgroup. Furthermore, the thickness of the intima was found to negatively correlate with the expression of Nogo-B in the intima and media (r = -0.32; p < 0.05; r = -0.32; p < 0.05). Macrophage infiltrates were more prominent in intima of CVR subjects (0.65 vs 3.52 a.u.; p < 0.01). Macrophage density in intima increased with atherosclerosis progression (r = 0.37; p < 0.01). CD68 macrophages density in adventitia was lower in CVR arteries than in healthy arteries. The expression of Nogo-B, in arterial intima, is impeded in the early stages of atherosclerosis. Accumulation of arterial intimal CD68 macrophages has been shown to progress; however, the overall macrophage density in the adventitia is reduced in arteries shown to have intimal thickening. Macrophage infiltration is not accompanied by Nogo-B expression in atherosclerotic arteries.
Nogo-B（网状蛋白4B）被认为是一种新型血管标志物，它可能在损伤诱导的内膜形成和动脉粥样硬化中发挥保护作用。研究发现，Nogo A/B在急性炎症中对单核细胞/巨噬细胞的募集至关重要，且在CD68 +巨噬细胞中表达。我们推测动脉粥样硬化中的巨噬细胞浸润不依赖于动脉壁中Nogo-B的表达。我们评估了健康器官捐献者和有心血管危险因素的器官捐献者髂动脉中Nogo-B的表达和巨噬细胞的聚集情况。研究了来自44名已故器官捐献者（17名女性和27名男性）的66条髂动脉的石蜡切片。创建了健康组和心血管风险（CVR）亚组。关于动脉粥样硬化进程的分期，在苏木精和伊红（H+E）染色组织切片的数字化图像中测量动脉内膜的厚度。对所有动脉（66个样本）进行免疫组织化学反应（检测Nogo-B和CD68）。对选定的动脉进行蛋白质免疫印迹法（WB，19个样本）和实时聚合酶链反应（27个样本）。使用免疫组织化学方法显示，健康受试者亚组内膜中的Nogo-B表达显著更高。蛋白质免疫印迹法和实时聚合酶链反应显示，CVR亚组外膜中的Nogo-B表达有降低趋势。此外，发现内膜厚度与内膜和中膜中Nogo-B的表达呈负相关（r = -0.32；p < 0.05；r = -0.32；p < 0.05）。CVR受试者内膜中的巨噬细胞浸润更为明显（0.65相对3.52任意单位；p < 0.01）。内膜中的巨噬细胞密度随动脉粥样硬化进展而增加（r = 0.37；p < 0.01）。CVR动脉外膜中的CD68巨噬细胞密度低于健康动脉。在动脉粥样硬化的早期阶段，动脉内膜中Nogo-B的表达受到抑制。已显示动脉内膜CD68巨噬细胞的聚集会进展；然而，在显示有内膜增厚的动脉中，外膜中的总体巨噬细胞密度降低。在动脉粥样硬化动脉中巨噬细胞浸润并不伴随Nogo-B表达。
