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Chemerin inhibits vascular calcification through ChemR23 and is associated with lower coronary calcium in chronic kidney disease.
Journal of Internal Medicine ( IF 9.0 ) Pub Date : 2019-07-07 , DOI: 10.1111/joim.12940
M Carracedo 1 , A Witasp 2 , A R Qureshi 2 , A Laguna-Fernandez 1 , T Brismar 3 , P Stenvinkel 2 , M Bäck 1, 4
Journal of Internal Medicine ( IF 9.0 ) Pub Date : 2019-07-07 , DOI: 10.1111/joim.12940
M Carracedo 1 , A Witasp 2 , A R Qureshi 2 , A Laguna-Fernandez 1 , T Brismar 3 , P Stenvinkel 2 , M Bäck 1, 4
Affiliation
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BACKGROUND
Chemerin is an adipokine that signals through the G protein-coupled receptor ChemR23 and is associated with inflammation, glucose homeostasis, lipid metabolism and renal function, all of which strongly influence cardiovascular risk. However, elevated chemerin provides a survival advantage in patients with chronic kidney disease (CKD), but how this relates to the cardiovascular phenotype is unknown.
OBJECTIVES
The aim of the present study was to establish the association of chemerin with coronary calcification and to determine the effects of chemerin signalling, through ChemR23, in vascular smooth muscle cell (VSMC) calcification.
METHODS
Plasma chemerin was measured in 113 patients with CKD and 50 healthy controls. All patients underwent computed tomography to determine coronary artery calcium (CAC) score. VSMCs were isolated from wild-type and ChemR23 knock-out mice and treated with chemerin.
RESULTS
Multivariate analyses established creatinine, cholesterol, body mass index and tumour necrosis factor as significant confounders for circulating chemerin levels. Despite these positive associations with renal function, cardiometabolic risk factors and inflammation, chemerin was inversely associated with CAC both in an age- and sex-adjusted analysis and in a multivariate analysis adjusting for the aforementioned confounders. In addition, circulating chemerin levels were associated with the calcification inhibitors matrix gla protein (MGP) and fetuin-A. Finally, chemerin significantly reduced phosphate-induced calcification and increased MGP expression in VSMCs, whereas chemerin was devoid of these effects in VSMCs lacking ChemR23.
CONCLUSION
In conclusion, these results suggest that chemerin signalling through ChemR23 in VSMCs protects against vascular calcification in CKD.
中文翻译：
Chemerin通过ChemR23抑制血管钙化，并与慢性肾脏疾病中较低的冠状动脉钙离子有关。
背景技术Chemerin是一种脂肪因子，它通过G蛋白偶联受体ChemR23发出信号，并与炎症，葡萄糖稳态，脂质代谢和肾功能有关，所有这些都强烈影响心血管疾病的风险。然而，升高的凯莫瑞在慢性肾脏病（CKD）患者中提供了生存优势，但是如何与心血管表型相关仍是未知的。目的本研究的目的是建立chemerin与冠状动脉钙化的联系，并确定chemerin信号通过ChemR23在血管平滑肌细胞（VSMC）钙化中的作用。方法测定113例CKD患者和50例健康对照者的血浆chemerin水平。所有患者均进行了计算机断层扫描，以确定冠状动脉钙（CAC）评分。从野生型和ChemR23基因敲除小鼠中分离VSMC，并用凯莫瑞处理。结果多元分析确定了肌酐，胆固醇，体重指数和肿瘤坏死因子是循环凯莫瑞水平的重要混杂因素。尽管这些与肾功能，心脏代谢危险因素和炎症呈正相关，但在针对年龄和性别进行调整的分析以及针对上述混杂因素进行调整的多变量分析中，凯莫瑞与CAC呈负相关。此外，循环中的凯莫瑞水平与钙化抑制剂基质gla蛋白（MGP）和胎球蛋白A有关。最后，凯莫瑞在VSMC中显着减少了磷酸盐诱导的钙化并增加了MGP表达，而凯莫瑞在缺乏ChemR23的VSMC中没有这些作用。
更新日期：2019-07-08
中文翻译：
Chemerin通过ChemR23抑制血管钙化，并与慢性肾脏疾病中较低的冠状动脉钙离子有关。
背景技术Chemerin是一种脂肪因子，它通过G蛋白偶联受体ChemR23发出信号，并与炎症，葡萄糖稳态，脂质代谢和肾功能有关，所有这些都强烈影响心血管疾病的风险。然而，升高的凯莫瑞在慢性肾脏病（CKD）患者中提供了生存优势，但是如何与心血管表型相关仍是未知的。目的本研究的目的是建立chemerin与冠状动脉钙化的联系，并确定chemerin信号通过ChemR23在血管平滑肌细胞（VSMC）钙化中的作用。方法测定113例CKD患者和50例健康对照者的血浆chemerin水平。所有患者均进行了计算机断层扫描，以确定冠状动脉钙（CAC）评分。从野生型和ChemR23基因敲除小鼠中分离VSMC，并用凯莫瑞处理。结果多元分析确定了肌酐，胆固醇，体重指数和肿瘤坏死因子是循环凯莫瑞水平的重要混杂因素。尽管这些与肾功能，心脏代谢危险因素和炎症呈正相关，但在针对年龄和性别进行调整的分析以及针对上述混杂因素进行调整的多变量分析中，凯莫瑞与CAC呈负相关。此外，循环中的凯莫瑞水平与钙化抑制剂基质gla蛋白（MGP）和胎球蛋白A有关。最后，凯莫瑞在VSMC中显着减少了磷酸盐诱导的钙化并增加了MGP表达，而凯莫瑞在缺乏ChemR23的VSMC中没有这些作用。
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