Increased levels of the homeostatic chemokine CXCL13 in human atherosclerosis - Potential role in plaque stabilization
Increased levels of the homeostatic chemokine CXCL13 in human atherosclerosis - Potential role in plaque stabilization
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DOI：
10.1016/j.atherosclerosis.2012.06.071
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发表时间：
2012-09-01
期刊：
影响因子：
5.3
通讯作者：
Aukrust, Pal
中科院分区：
文献类型：
--
作者：
Smedbakken, Linda M.;Halvorsen, Bente;Aukrust, Pal
目的：基于新认识的稳态趋化因子在炎症中的作用，我们假设 CXCL13 可以调节动脉粥样硬化形成和斑块不稳定。方法：该研究包括颈动脉粥样硬化患者的体内分析和参与动脉粥样硬化形成的细胞（即单核细胞/巨噬细胞、血管平滑肌细胞 [SMC] 和血小板）的体外实验。结果：我们的主要发现是：（i）颈动脉粥样硬化 (n = 130) 导致血浆 CXCL13 水平升高，在有症状的疾病中水平尤其高。 (ii)与非动脉粥样硬化血管相比，CXCL13在动脉粥样硬化颈动脉斑块内表现出表达增加。 (iii)在动脉粥样硬化病变内，CXCR5和CXCL13在斑块进展的所有阶段由巨噬细胞和SMC表达。 (iv)活化血小板的释放和Toll样受体的活化增强了THP-1单核细胞和原代单核细胞中CXCL13的表达。 (v) 在体外，CXCL13 在原代单核细胞、THP-1 巨噬细胞和血管 SMC 中发挥抗凋亡作用。 (vi)CXCL13增加THP-1细胞和分离的颈动脉斑块样品中精氨酸酶-1、转化生长因子-β和白细胞介素-10的表达。结论：颈动脉粥样硬化中CXCL13的水平在全身和动脉粥样硬化病变内增加。根据我们的体外研究结果，我们假设 CXCL13-CXCR5 相互作用具有潜在的斑块稳定作用。 (c) 2012 Elsevier Ireland Ltd. 保留所有权利。
Objectives: Based on the newly recognized role of the homeostatic chemokines in inflammation, we hypothesized that CXCL13 could modulate atherogenesis and plaque destabilization.Methods: The study included in vivo analyses in patients with carotid atherosclerosis and in vitro experiments in cells involved in atherogenesis (ie, monocytes/macrophages, vascular smooth muscle cells [SMC], and platelets).Results: Our main findings were: (i) Patients with carotid atherosclerosis (n = 130) had increased plasma levels of CXCL13 with particularly high levels in symptomatic disease. (ii) CXCL13 showed increased expression within atherosclerotic carotid plaques as compared with non-atherosclerotic vessels. (iii) Within the atherosclerotic lesions, CXCR5 and CXCL13 were expressed by macrophages and SMC in all stages of plaque progression. (iv) Releasate from activated platelets and toll-like receptor activation enhanced the expression of CXCL13 in THP-1 monocytes and primary monocytes. (v) In vitro, CXCL13 exerted anti-apoptotic effects in primary monocytes, THP-1 macrophages, and vascular SMC. (vi) CXCL13 increased arginase-1, transforming growth factor-beta, and interleukin-10 expression in THP-1 cells and in samples from isolated carotid plaques.Conclusion: Levels of CXCL13 are increased in carotid atherosclerosis both systemically and within the atherosclerotic lesion. Based on our in vitro findings, we hypothesize a potential plaque stabilizing effects of CXCL13-CXCR5 interaction. (c) 2012 Elsevier Ireland Ltd. All rights reserved.