类风湿关节炎中的前蛋白转化酶枯草杆菌蛋白酶/kexin 9型

Proprotein convertase subtilisin/kexin type 9 in rheumatoid arthritis.

作者信息

Ferraz-Amaro Ivan, López-Mejías Raquel, Ubilla Begoña, Genre Fernanda, Tejera-Segura Beatriz, de Vera-González Antonia M, González-Rivero Agustín F, Olmos Jose M, Hernández Jose L, Llorca Javier, González-Gay Miguel A

机构信息

Division of Rheumatology, Hospital Universitario de Canarias, Tenerife, Spain.

Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.

出版信息

Clin Exp Rheumatol. 2016 Nov-Dec;34(6):1013-1019. Epub 2016 Aug 31.

PMID:27606890

Abstract

OBJECTIVES

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation and that has been linked with cardiovascular risk. The purpose of the present study was to examine whether PCSK9 levels are related to both abnormalities in the lipid profile and the severe atherosclerosis that occur in rheumatoid arthritis (RA) patients.

METHODS

Cross-sectional study that encompassed 520 individuals; 326 patients with RA and 194 age- and sex-matched controls. PCSK9 and lipoproteins serum concentrations, standard lipid profile and carotid intima-media thickness (cIMT) and carotid plaques were assessed in patients and controls. A multivariable analysis, adjusted for standard cardiovascular risk factors, was performed to evaluate the influence of PCSK9 on RA related dyslipidaemia and subclinical carotid atherosclerosis.

RESULTS

After adjusting for classical cardiovascular risk factors, lipid profile and statins, RA patients showed lower PCSK9 serum concentrations than controls (beta coefficient -45 95%CI [-53, -38] ng/ml, p=0.00). PCSK9 was associated with both cIMT and the presence of carotid plaques in RA patients. However, this association was lost after adjusting for classical cardiovascular risk factors.

CONCLUSIONS

PCSK9 is down-regulated in patients with RA.

摘要

目的

前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）是一种丝氨酸蛋白酶，通过低密度脂蛋白受体降解来调节胆固醇代谢，并且与心血管风险相关。本研究的目的是检验PCSK9水平是否与类风湿关节炎（RA）患者出现的血脂异常和严重动脉粥样硬化均相关。

方法

横断面研究纳入了520名个体；326例RA患者和194名年龄及性别匹配的对照者。对患者和对照者评估了PCSK9和脂蛋白血清浓度、标准血脂谱、颈动脉内膜中层厚度（cIMT）以及颈动脉斑块。进行了一项针对标准心血管危险因素进行校正的多变量分析，以评估PCSK9对RA相关血脂异常和亚临床颈动脉粥样硬化的影响。