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血浆胱抑素 C-脂联素复合物与冠状动脉斑块不稳定相关。

Cystatin C-Adiponectin Complex in Plasma Associates with Coronary Plaque Instability.

机构信息

Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine.

Department of Cardiology, Hyogo Prefectural Nishinomiya Hospital.

出版信息

J Atheroscler Thromb. 2017 Sep 1;24(9):970-979. doi: 10.5551/jat.39545. Epub 2017 Mar 17.

Abstract

AIM

Adiponectin (APN) is an adipocyte-derived bioactive molecule with antiatherogenic properties. We previously reported that cystatin C (CysC) abolished the anti-atherogenic effects of APN. We aimed to elucidate the clinical significance of CysC-APN complex in patients with coronary artery disease (CAD).

METHODS

We enrolled 43 stable CAD male patients to examine the relationship between CysC-APN complex and coronary plaque characteristics. Serum was immunoprecipitated by the anti-APN antibody and immunoblotted by the anti-CysC antibody to demonstrate the presence of CysC-APN complexes in vivo. To confirm their binding in vitro, HEK293T cell lysates overexpressing myc-APN and FLAG-CysC were immunoprecipitated with an anti-myc or anti-FLAG antibody, followed by immunoblotting with an anti-APN or anti-CysC antibody.

RESULTS

CysC was identified as a specific co-immunoprecipitant with APN by the anti-APN antibody in human serum. In vitro, FLAG-CysC was co-immunoprecipitated with myc-APN by the anti-myc antibody and myc-APN was co-immunoprecipitated with FLAG-CysC by the anti-FLAG antibody. Among CAD patients, serum CysC-APN complex levels negatively correlated with fibrotic components of coronary plaques and positively correlated with either necrotic or lipidic plus necrotic components. Plaque burden negatively correlated with serum APN levels but not serum CysC-APN complex levels. Serum CysC levels had no association with plaque characteristics. In multivariate analysis, CysC-APN complex levels were identified as the strongest negative factor for fibrotic components and the strongest positive factor for both necrotic and lipidic plus necrotic components.

CONCLUSION

Measuring serum CysC-APN complex levels is helpful for evaluating coronary plaque instability in CAD patients.

摘要

目的

脂联素(APN)是一种具有抗动脉粥样硬化特性的脂肪细胞衍生的生物活性分子。我们之前的研究表明,半胱氨酸蛋白酶抑制剂 C(CysC)会消除 APN 的抗动脉粥样硬化作用。本研究旨在阐明 CysC-APN 复合物在冠心病(CAD)患者中的临床意义。

方法

我们纳入了 43 例稳定型 CAD 男性患者,以检验 CysC-APN 复合物与冠状动脉斑块特征之间的关系。用抗 APN 抗体对血清进行免疫沉淀,再用抗 CysC 抗体进行免疫印迹,以证明体内存在 CysC-APN 复合物。为了在体外确认它们的结合,用抗 myc 或抗 FLAG 抗体对过表达 myc-APN 和 FLAG-CysC 的 HEK293T 细胞裂解物进行免疫沉淀,然后用抗 APN 或抗 CysC 抗体进行免疫印迹。

结果

用抗 APN 抗体从人血清中鉴定出 CysC 是 APN 的特异性共免疫沉淀物。在体外,FLAG-CysC 被抗 myc 抗体共免疫沉淀,myc-APN 被抗 FLAG 抗体共免疫沉淀。在 CAD 患者中,血清 CysC-APN 复合物水平与冠状动脉斑块的纤维成分呈负相关,与坏死或脂质加坏死成分呈正相关。斑块负荷与血清 APN 水平呈负相关,但与血清 CysC-APN 复合物水平无关。血清 CysC 水平与斑块特征无关。在多变量分析中,CysC-APN 复合物水平被确定为纤维成分的最强负因素,也是坏死和脂质加坏死成分的最强正因素。

结论

检测血清 CysC-APN 复合物水平有助于评估 CAD 患者的冠状动脉斑块不稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3026/5587523/bcf958b7a406/jat-24-970-g001.jpg

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