Grönberg Caitríona, Bengtsson Eva, Fredrikson Gunilla Nordin, Nitulescu Mihaela, Asciutto Giuseppe, Persson Ana, Andersson Linda, Nilsson Jan, Gonçalves Isabel, Björkbacka Harry
From the Department of Clinical Sciences (C.G., E.B., G.N.F., M.N., A.P., L.A., J.N., I.G., H.B.) and Vascular Centre Malmö-Lund (G.A.), Skåne University Hospital, Malmö, Lund University, Lund, Sweden.
Stroke. 2015 Oct;46(10):2748-54. doi: 10.1161/STROKEAHA.115.009910. Epub 2015 Sep 1.
Interleukin-16 (IL-16) functions as a regulator of T-cell growth and acts as an inducer of cell migration. The aim of this study was to determine whether IL-16 measured in human carotid plaques was associated with symptoms (eg, stroke, transient ischemic attack, or amaurosis fugax), markers of plaque stability, and postoperative cardiovascular events.
Plaques obtained from patients who had ≥1 cerebrovascular ischemic events within 1 month before endarterectomy (n=111) were compared with plaques from patients without symptoms (n=95). Neutral lipids, smooth muscle cell, and macrophage contents were evaluated histologically, and collagen, elastin, and caspase-3 activity were measured biochemically. IL-16, matrix metalloproteinases, and tissue inhibitors of metalloproteinases were measured in plaque homogenates using a multiplex immunoassay. IL-16, CD3, CD4, and FoxP3 mRNA expressions in carotid plaques were analyzed with quantitative real-time polymerase chain reaction.
Carotid plaques from asymptomatic patients had higher levels of IL-16 mRNA. High plaque IL-16 protein levels (above median) were associated with reduced incidence of postoperative cardiovascular events during a mean follow-up of 21 months (hazard ratio, 0.47; 95% confidence interval, 0.22-0.99; P=0.047). IL-16 levels correlated with the plaque-stabilizing components: elastin, collagen, matrix metalloproteinase-2, tissue inhibitors of metalloproteinase-1, tissue inhibitors of metalloproteinase-2 and FoxP3 mRNA.
This study shows that high levels of IL-16 are associated with asymptomatic carotid plaques, expression of factors contributing to plaque stability, and decreased risk of new cardiovascular events during a 2-year period after surgery, suggesting that IL-16 might have a protective role in human atherosclerotic disease.
白细胞介素 - 16(IL - 16)作为T细胞生长的调节剂,并作为细胞迁移的诱导剂。本研究的目的是确定在人类颈动脉斑块中检测到的IL - 16是否与症状(如中风、短暂性脑缺血发作或一过性黑矇)、斑块稳定性标志物以及术后心血管事件相关。
将在动脉内膜切除术前行内膜剥脱术的患者(n = 111)在1个月内发生≥1次脑血管缺血事件的患者的斑块,与无症状患者的斑块(n = 95)进行比较。通过组织学评估中性脂质、平滑肌细胞和巨噬细胞含量,并通过生化方法测量胶原蛋白、弹性蛋白和半胱天冬酶 - 3活性。使用多重免疫测定法在斑块匀浆中测量IL - 16、基质金属蛋白酶和金属蛋白酶组织抑制剂。采用定量实时聚合酶链反应分析颈动脉斑块中IL - 16、CD3、CD4和FoxP3 mRNA的表达。
无症状患者的颈动脉斑块中IL - 16 mRNA水平较高。在平均21个月的随访期间,高斑块IL - 16蛋白水平(高于中位数)与术后心血管事件发生率降低相关(风险比,0.47;95%置信区间,0.22 - 0.99;P = 0.047)。IL - 16水平与斑块稳定成分相关:弹性蛋白、胶原蛋白、基质金属蛋白酶 - 2、金属蛋白酶组织抑制剂 - 1、金属蛋白酶组织抑制剂 - 2和FoxP3 mRNA。
本研究表明,高水平的IL - 16与无症状颈动脉斑块、有助于斑块稳定的因素的表达以及术后2年内新的心血管事件风险降低相关,提示IL - 16可能在人类动脉粥样硬化疾病中具有保护作用。