University of Michigan, Ann Arbor.
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland.
Arthritis Rheumatol. 2020 Jan;72(1):20-30. doi: 10.1002/art.41059. Epub 2019 Nov 26.
Systemic lupus erythematosus (SLE) patients exhibit accelerated development of atherosclerosis and increased incidents of cardiovascular disease (CVD) that cannot be explained by traditional risk factors alone. Accumulating evidence suggests that reduced levels of high-density lipoproteins (HDLs), along with altered HDL composition and function, may contribute to the accelerated atherosclerosis in SLE patients. Normally, HDLs play various atheroprotective roles through facilitating cholesterol efflux, inhibiting vascular inflammation, and scavenging oxidative species. However, systemic inflammation, oxidative stress, and autoimmunity in SLE patients induce changes in HDL size distribution and proteomic and lipidomic signatures. These compositional changes in HDLs result in the formation of proinflammatory, dysfunctional HDL. These lupus-altered HDLs have impaired antiatherogenic function with reduced cholesterol efflux capacities, impaired antioxidation abilities, and diminished antiinflammatory properties. In fact, dysfunctional HDL may promote atherogenesis by inducing inflammation. Thus, dysfunctional HDLs could be an important biomarker of accelerated atherosclerosis in lupus. Additionally, HDL-targeted therapies, especially infusion of reconstituted HDLs, may serve as a potential therapeutic intervention for SLE patients with CVD.
系统性红斑狼疮 (SLE) 患者表现出动脉粥样硬化的加速发展和心血管疾病 (CVD) 的发生率增加，这些不能仅用传统的危险因素来解释。越来越多的证据表明，高密度脂蛋白 (HDL) 水平降低，以及 HDL 组成和功能的改变，可能导致 SLE 患者的动脉粥样硬化加速。正常情况下，HDL 通过促进胆固醇流出、抑制血管炎症和清除氧化物质来发挥多种抗动脉粥样硬化作用。然而，SLE 患者的全身炎症、氧化应激和自身免疫会引起 HDL 大小分布和蛋白质组学及脂质组学特征的变化。这些 HDL 的组成变化导致促炎、功能失调的 HDL 的形成。这些狼疮改变的 HDL 具有受损的抗动脉粥样硬化功能，胆固醇流出能力降低、抗氧化能力受损和抗炎特性减弱。事实上，功能失调的 HDL 可能通过诱导炎症而促进动脉粥样硬化形成。因此，功能失调的 HDL 可能是狼疮患者动脉粥样硬化加速的一个重要生物标志物。此外，针对 HDL 的治疗方法，特别是重组成分 HDL 的输注，可能成为 CVD 狼疮患者的一种潜在治疗干预措施。
