Sánchez-Pérez Hiurma, Quevedo-Abeledo Juan C, Tejera-Segura Beatriz, de Armas-Rillo Laura, Rúa-Figueroa Iñigo, González-Gay Miguel A, Ferraz-Amaro Iván
Division of Rheumatology, Hospital Universitario de Canarias, Tenerife, Spain.
Division of Rheumatology, Hospital Doctor Negrín, Las Palmas de Gran Canaria, Spain.
Ther Adv Musculoskelet Dis. 2020 Nov 28;12:1759720X20975904. doi: 10.1177/1759720X20975904. eCollection 2020.
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 to cardiovascular (CV) disease. The purpose of the present study was to examine whether PCSK9 levels are disrupted compared with controls in patients with systemic lupus erythematosus (SLE). We additionally sought to establish whether PCSK9 is related to both the abnormalities in the lipid profile and to the disease activity or damage of patients with SLE.
We performed a cross-sectional study that encompassed 366 individuals: 195 SLE patients and 171 age-, sex-, and statin intake-matched controls. PCSK9, lipoproteins serum concentrations, and lipid profiles were assessed in patients and controls. A multivariable analysis, adjusted for standard CV risk factors, was performed to evaluate the role of PCSK9 in SLE-related dyslipidemia.
Most lipid related-molecules were decreased in patients with SLE compared with controls. This downregulation included PCSK9, with PCSK9 levels being lower in patients than controls in the full multivariable analysis, including the modifications in lipid profiles that the disease itself produces {beta coefficient -73 [95% confidence interval (CI) -91 to -54] ng/ml, ⩽ 0.001}. Both SLICC and SLEDAI scores were independently and positively related to PCSK9. Patients currently on hydroxychloroquine exhibited decreased levels of PCSK9 compared with those that were not taking hydroxychloroquine [beta coefficient -30 (95% CI -54 to -6) ng/ml, = 0.015].
PCSK9 is downregulated in SLE compared with controls, but SLE patients with higher disease activity and damage exhibited higher PSCK9 serum levels.
前蛋白转化酶枯草溶菌素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（CV）疾病有关。本研究的目的是检查系统性红斑狼疮（SLE）患者与对照组相比，PCSK9水平是否受到破坏。我们还试图确定PCSK9是否与SLE患者的血脂异常以及疾病活动或损害有关。
我们进行了一项横断面研究，纳入366名个体：195名SLE患者和171名年龄、性别和他汀类药物摄入相匹配的对照组。对患者和对照组进行了PCSK9、脂蛋白血清浓度和血脂谱评估。进行了一项针对标准CV危险因素进行调整的多变量分析，以评估PCSK9在SLE相关血脂异常中的作用。
与对照组相比，SLE患者中大多数与脂质相关的分子减少。这种下调包括PCSK9，在全多变量分析中，患者的PCSK9水平低于对照组，包括疾病本身产生的血脂谱变化{β系数 -73 [95%置信区间（CI）-91至-54] ng/ml，P⩽0.001}。SLICC和SLEDAI评分均与PCSK9独立且呈正相关。目前服用羟氯喹的患者与未服用羟氯喹的患者相比，PCSK9水平降低[β系数 -30（95% CI -54至-6）ng/ml，P = 0.015]。
与对照组相比，SLE患者的PCSK9水平下调，但疾病活动和损害较高的SLE患者血清PCSK9水平较高。
