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循环细胞因子与冠状动脉粥样硬化的程度及成分的关系:来自动脉粥样硬化斑块消退-IVUS研究的结果

Circulating cytokines in relation to the extent and composition of coronary atherosclerosis: results from the ATHEROREMO-IVUS study.

作者信息

Battes Linda C, Cheng Jin M, Oemrawsingh Rohit M, Boersma Eric, Garcia-Garcia Hector M, de Boer Sanneke P M, Buljubasic Nermina, Mieghem Nicolas A van, Regar Evelyn, Geuns Robert-Jan van, Serruys Patrick W, Akkerhuis K Martijn, Kardys Isabella

机构信息

Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.

Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.

出版信息

Atherosclerosis. 2014 Sep;236(1):18-24. doi: 10.1016/j.atherosclerosis.2014.06.010. Epub 2014 Jun 26.

Abstract

OBJECTIVE

We investigated whether concentrations of TNF-α, TNF-β, TNF-receptor 2, interferon-γ, IL-6, IL-8, IL-10 and IL-18 are associated with extent and composition of coronary atherosclerosis determined by grayscale and virtual histology (VH)- intravascular ultrasound (IVUS).

METHODS

Between 2008 and 2011, IVUS(-VH) imaging of a non-culprit coronary artery was performed in 581 patients (stable angina pectoris (SAP), n = 261; acute coronary syndrome (ACS), n = 309) undergoing coronary angiography from the ATHEROREMO-IVUS study. Plaque burden, presence of VH-IVUS-derived thin-cap fibroatheroma (TCFA) lesions, and presence of VH-TCFA lesions with plaque burden ≥70% were assessed. Blood samples for cytokine measurement were drawn from the arterial sheath prior to the angiography procedure. We applied linear and logistic regression.

RESULTS

TNF-α levels were positively associated with plaque burden (beta (β) [95%CI]: 4.45 [0.99-7.91], for highest vs lowest TNF-α tertile) and presence of VH-TCFA lesions (odds ratio (OR) [95%CI] 2.30 (1.17-4.52), highest vs lowest TNF-α tertile) in SAP patients. Overall, an inverse association was found between IL-10 concentration and plaque burden (β [95%CI]: -1.52 [-2.49 to -0.55], per Ln (pg/mL) IL-10) as well as IL-10 and VH-TCFA lesions with plaque burden ≥70% (OR: 0.31 [0.12-0.80],highest vs lowest IL-10 tertile). These effects did not reach statistical significance in the separate SAP and ACS groups.

CONCLUSION

Higher circulating TNF-α was associated with higher plaque burden and VH-TCFA lesions in SAP patients. Lower circulating IL-10 was associated with higher plaque burden and large VH-TCFA lesions. These in-vivo findings suggest a role for these cytokines in extent and vulnerability of atherosclerosis.

摘要

目的

我们研究了肿瘤坏死因子-α(TNF-α)、肿瘤坏死因子-β(TNF-β)、肿瘤坏死因子受体2、干扰素-γ、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)和白细胞介素-18(IL-18)的浓度是否与通过灰阶和虚拟组织学(VH)血管内超声(IVUS)确定的冠状动脉粥样硬化的范围和成分相关。

方法

在2008年至2011年期间,对来自ATHEROREMO-IVUS研究的581例接受冠状动脉造影的患者(稳定型心绞痛(SAP),n = 261;急性冠状动脉综合征(ACS),n = 309)的非罪犯冠状动脉进行了IVUS(-VH)成像。评估了斑块负荷、VH-IVUS衍生的薄帽纤维粥样瘤(TCFA)病变的存在情况以及斑块负荷≥70%的VH-TCFA病变的存在情况。在血管造影术前从动脉鞘中采集用于细胞因子测量的血样。我们应用了线性和逻辑回归分析。

结果

在SAP患者中,TNF-α水平与斑块负荷呈正相关(β[95%置信区间]:4.45[0.99 - 7.91],最高三分位数与最低三分位数的TNF-α相比)以及与VH-TCFA病变的存在相关(优势比(OR)[95%置信区间]2.30(1.17 - 4.52),最高三分位数与最低三分位数的TNF-α相比)。总体而言,发现IL-10浓度与斑块负荷之间呈负相关(β[95%置信区间]:-1.52[-2.49至-0.55],每Ln(pg/mL)IL-10)以及IL-10与斑块负荷≥70%的VH-TCFA病变之间呈负相关(OR:0.31[0.12 - 0.80],最高三分位数与最低三分位数的IL-10相比)。这些效应在单独的SAP和ACS组中未达到统计学意义。

结论

在SAP患者中,循环中较高的TNF-α与较高的斑块负荷和VH-TCFA病变相关。循环中较低的IL-10与较高的斑块负荷和大的VH-TCFA病变相关。这些体内研究结果表明这些细胞因子在动脉粥样硬化的范围和易损性中起作用。

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