脂联素-2 以阶段依赖的方式促进实验性动脉粥样硬化。
Lipocalin-2 contributes to experimental atherosclerosis in a stage-dependent manner.
机构信息
Division of Biotherapeutics, LACDR, Leiden University, Einsteinweg 55, 2333CC, Leiden, The Netherlands.
Division of Biotherapeutics, LACDR, Leiden University, Einsteinweg 55, 2333CC, Leiden, The Netherlands.
出版信息
Atherosclerosis. 2018 Aug;275:214-224. doi: 10.1016/j.atherosclerosis.2018.06.015. Epub 2018 Jun 13.
BACKGROUND AND AIMS
Lipocalin-2 (Lcn2) is a glycoprotein which can be secreted by immune cells. Several studies in humans have suggested Lcn2 can be used as a biomarker for the detection of unstable atherosclerotic lesions, partly as it is known to interact with MMP-9.
METHODS
In this study, we generated LdlrLcn2 mice to assess the functional role of Lcn2 in different stages of atherosclerosis. Atherosclerotic lesions were characterized through histological analysis and myeloid cell populations were examined using flow cytometry.
RESULTS
We show that LdlrLcn2 mice developed larger atherosclerotic lesions during earlier stages of atherosclerosis and had increased circulating Ly6C inflammatory monocytes compared to Ldlr mice. Advanced atherosclerotic lesions from LdlrLcn2 mice had decreased necrotic core area, suggesting Lcn2 deficiency may affect lesion stability. Furthermore, MMP-9 activity was diminished in plaques from LdlrLcn2 mice.
CONCLUSIONS
Altogether, these findings suggest that Lcn2 deficiency promotes lesion growth in earlier stages of the disease while it decreases MMP-9 activity and necrotic core size in advanced atherosclerosis.
背景与目的
脂联素-2（Lcn2）是一种可以由免疫细胞分泌的糖蛋白。多项人类研究表明，Lcn2 可以作为不稳定动脉粥样硬化病变的检测生物标志物，部分原因是它已知与 MMP-9 相互作用。
方法
在本研究中，我们生成了 LdlrLcn2 小鼠，以评估 Lcn2 在动脉粥样硬化不同阶段的功能作用。通过组织学分析对动脉粥样硬化病变进行了特征描述，并使用流式细胞术检查了髓样细胞群体。
结果
我们发现，LdlrLcn2 小鼠在动脉粥样硬化的早期阶段发展出更大的动脉粥样硬化病变，并且与 Ldlr 小鼠相比，循环 Ly6C 炎性单核细胞增加。LdlrLcn2 小鼠的晚期动脉粥样硬化病变的坏死核心面积减少，提示 Lcn2 缺乏可能影响病变的稳定性。此外，LdlrLcn2 小鼠斑块中的 MMP-9 活性降低。
结论
总之，这些发现表明，Lcn2 缺乏促进疾病早期阶段的病变生长，同时降低 MMP-9 活性和晚期动脉粥样硬化中的坏死核心大小。
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