Arida Aikaterini, Legaki Aigli-Ioanna, Kravvariti Evrydiki, Protogerou Athanasios, Sfikakis Petros P, Chatzigeorgiou Antonios
Joint Rheumatology Program, National and Kapodistrian University of Athens Medical School, Athens, Greece.
Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Front Cardiovasc Med. 2021 Oct 8;8:738764. doi: 10.3389/fcvm.2021.738764. eCollection 2021.
Rheumatoid arthritis (RA) is associated with the emergence of cardiovascular disease, while chronic inflammation is considered a common denominator for their parallel progression. The Proprotein convertase subtilisin/kexin type 9 (PCSK9)/LDL-Receptor (LDLR) system is of high importance during atherogenesis, via regulating the clearance of LDL from the circulation; nevertheless the role of this molecular mechanism during RA-related atheromatosis is not known. Herein, high-resolution ultrasound measurements for arterial hypertrophy, atheromatosis and arterial stiffness as well as comprehensive biochemical profiling were performed in 85 RA patients. The circulating levels of PCSK9 and LDLR were measured and their potential associations as well as of the PCSK9/LDLR ratio with patients' characteristics and the degree of atherosclerosis were investigated. Increased LDLR levels and decreased PCSK9/LDLR ratio were found in RA patients with at least 2 atheromatic plaques as compared to the ones without any plaques. In addition the levels of both PCSK9 and LDLR were positively correlated with the presence of atheromatic plaques as an age- and gender- adjusted multivariate analysis revealed. Our data imply that the PCSK9/LDLR system plays a significant role during RA-related atherosclerosis and may therefore be used as a screening tool for disease progression in the future.
类风湿性关节炎（RA）与心血管疾病的发生有关，而慢性炎症被认为是它们平行进展的共同因素。前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK9）/低密度脂蛋白受体（LDLR）系统在动脉粥样硬化形成过程中通过调节循环中低密度脂蛋白的清除起重要作用；然而，这种分子机制在RA相关动脉粥样硬化中的作用尚不清楚。在此，对85例RA患者进行了动脉肥厚、动脉粥样硬化和动脉僵硬度的高分辨率超声测量以及全面的生化分析。测量了PCSK9和LDLR的循环水平，并研究了它们之间的潜在关联以及PCSK9/LDLR比值与患者特征和动脉粥样硬化程度的关系。与无任何斑块的RA患者相比，至少有2个动脉粥样硬化斑块的RA患者LDLR水平升高，PCSK9/LDLR比值降低。此外，年龄和性别校正的多变量分析显示，PCSK9和LDLR水平均与动脉粥样硬化斑块的存在呈正相关。我们的数据表明，PCSK9/LDLR系统在RA相关动脉粥样硬化中起重要作用，因此未来可能用作疾病进展的筛查工具。
