Department of Vascular Medicine, University Medical Center Utrecht, The Netherlands.
Department of Cardio-thoracic surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
Atherosclerosis. 2014 Mar;233(1):242-7. doi: 10.1016/j.atherosclerosis.2013.12.005. Epub 2014 Jan 10.
Perivascular adipose tissue (pvAT) may induce a local pro-inflammatory environment, possibly contributing to coronary atherosclerosis. We investigated whether there is a difference in adipocytokine production by pvAT near stenotic and non-stenotic coronary artery segments in patients with coronary artery disease (CAD).
In patients undergoing CABG with or without valve replacement (n = 38) pvAT near stenotic and near non-stenotic coronary segments was harvested. PvAT was incubated ex vivo for 24h. Concentrations of 23 adipocytokines were measured in the supernatants with a Multiplex assay. The number of macrophages (CD68, CD11c, CD206) and lymphocytes (CD45) in pvAT was determined. Differences between stenosis and control pvAT were tested with Wilcoxon signed rank test corrected for multiple comparisons.
Production of IL-5, IL-1α, IL-17, IL-18 and IL-23 was higher in control than stenosis pvAT samples (p < 0.0021). Macrophages were more abundant in stenosis than in control pvAT (median n/400× field: 2.3 IQR: 0.3-4.5 versus 1.2 IQR: 0.1-2.5). There was a predominance of M2 macrophages in both stenosis and control pvAT (median n/400× field: macrophages stenosis: M1: 0.0; M2: 1.0 p = 0.004; control: M1: 0.0; M2: 0.6 p = 0.013). The relation between adipocytokine production and macrophage infiltration was not different in stenosis and control pvAT.
In patients with CAD, multiple adipocytokines were secreted at higher levels by pvAT near non-stenotic than near stenotic coronary artery segments. Furthermore, pvAT macrophages are associated with stenosis of the adjacent vessel. M2 macrophages were more abundant than M1 macrophages in pvAT.
血管周脂肪组织(pvAT)可能会引起局部促炎环境,从而可能导致冠状动脉粥样硬化。我们研究了在患有冠状动脉疾病(CAD)的患者中,狭窄和非狭窄冠状动脉段附近的 pvAT 产生的细胞因子是否存在差异。
在接受 CABG 手术的患者中(伴或不伴瓣膜置换术),采集狭窄和非狭窄冠状动脉段附近的 pvAT。将 pvAT 进行离体孵育 24 小时。采用多重免疫分析方法检测上清液中 23 种细胞因子的浓度。通过 CD68、CD11c、CD206 测定 pvAT 中的巨噬细胞数量(CD11c、CD206)和淋巴细胞(CD45)。使用 Wilcoxon 符号秩检验,对校正后的多个比较进行测试,以检测狭窄与对照 pvAT 之间的差异。
IL-5、IL-1α、IL-17、IL-18 和 IL-23 在对照 pvAT 样本中的产生量高于狭窄 pvAT 样本(p<0.0021)。在狭窄 pvAT 中,巨噬细胞的含量多于对照 pvAT(中位数 n/400×视野:2.3 IQR:0.3-4.5 与 1.2 IQR:0.1-2.5)。在狭窄和对照 pvAT 中均以 M2 巨噬细胞为主(中位数 n/400×视野:狭窄 pvAT:M1:0.0;M2:1.0,p=0.004;对照 pvAT:M1:0.0;M2:0.6,p=0.013)。狭窄和对照 pvAT 中细胞因子产生与巨噬细胞浸润之间的关系无差异。
在患有 CAD 的患者中,与狭窄冠状动脉段附近的 pvAT 相比,非狭窄冠状动脉段附近的 pvAT 分泌多种细胞因子的水平更高。此外,pvAT 中的巨噬细胞与邻近血管的狭窄有关。在 pvAT 中,M2 巨噬细胞比 M1 巨噬细胞更丰富。