Atherosclerosis Laboratory, ANZAC Research Institute, Concord Repatriation General Hospital and the University of Sydney, Sydney, Australia.
Concord Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia; Collaborative Centre for Cardiometabolic Health, Charles Perkins Centre, University of Sydney, Sydney, Australia.
J Lipid Res. 2024 Jul;65(7):100577. doi: 10.1016/j.jlr.2024.100577. Epub 2024 Jun 13.
Patients with schizophrenia show a disproportionally increased risk of cardiovascular disease. Hypertriglyceridemia is prevalent in this population; however, how this relates to levels of remnant cholesterol, triglyceride (TG)-rich lipoprotein (TRL) particle size and composition, TG turnover, and apolipoprotein (apo) and angiopoietin-like protein (ANGPTL) concentrations is unknown. Fasting levels of cholesterol (total [TC], LDL-C, HDL-C, non-HDL-C and remnant cholesterol) and TG were determined in 110 patients diagnosed with schizophrenia, and 46 healthy controls. TRL particle size, concentration and composition, and β-hydroxybutyrate (TG turnover marker) were assessed by NMR. Levels of apoCII, apoCIII, apoE, ANGPTL3, ANGPTL4, and ANGPTL8 were measured by ELISA, and apoCII, apoCIII and apoE were further evaluated in HDL and non-HDL fractions. Patients with schizophrenia had significantly elevated TG, TG:apoB ratio, non-HDL-C, remnant cholesterol, non-HDL-apoCII and non-HDL-apoCIII, and HDL-apoE (all P < 0.05), lower HDL-C and apoA-I (all P < 0.001), and comparable apoB, TC, TC:apoB ratio, LDL-C, β-hydroxybutyrate, ANGPTL3, ANGPTL4 and ANGPTL8 to healthy controls. Patients had a 12.0- and 2.5-fold increase in the concentration of large and medium TRL particles respectively, but similar cholesterol:TG ratio within each particle. Plasma TG, remnant cholesterol, and large and medium TRL particle concentrations correlated strongly with apoCII, apoCIII, and apoE in the non-HDL fraction, and with apoCIII and apoE in the HDL fraction in patients with schizophrenia. Differences in TG, HDL-C, TRL particle concentrations, apoCIII, and apoE persisted after adjustment for conventional risk factors. These results are consistent with impaired TRL lipolysis and clearance in patients with schizophrenia which may be responsive to targeting apoCIII.
精神分裂症患者的心血管疾病风险不成比例地增加。该人群中普遍存在高甘油三酯血症；然而，这与残余胆固醇水平、甘油三酯（TG）丰富的脂蛋白（TRL）颗粒大小和组成、TG 周转率以及载脂蛋白（apo）和血管生成素样蛋白（ANGPTL）浓度有何关系尚不清楚。在 110 名被诊断患有精神分裂症的患者和 46 名健康对照者中，测定了空腹胆固醇（总胆固醇 [TC]、LDL-C、HDL-C、非 HDL-C 和残余胆固醇）和 TG 水平。通过 NMR 评估 TRL 颗粒大小、浓度和组成以及 β-羟基丁酸（TG 周转率标志物）。通过 ELISA 测量 apoCII、apoCIII、apoE、ANGPTL3、ANGPTL4 和 ANGPTL8 的水平，并进一步在 HDL 和非 HDL 级分中评估 apoCII、apoCIII 和 apoE。精神分裂症患者的 TG、TG:apoB 比值、非 HDL-C、残余胆固醇、非 HDL-apoCII 和非 HDL-apoCIII 以及 HDL-apoE 显著升高（均 P < 0.05），HDL-C 和 apoA-I 降低（均 P < 0.001），apoB、TC、TC:apoB 比值、LDL-C、β-羟基丁酸、ANGPTL3、ANGPTL4 和 ANGPTL8 与健康对照组相比无差异。患者的大、中 TRL 颗粒浓度分别增加了 12.0 倍和 2.5 倍，但每个颗粒中的胆固醇:TG 比值相似。精神分裂症患者的血浆 TG、残余胆固醇和大、中 TRL 颗粒浓度与非 HDL 级分中的 apoCII、apoCIII 和 apoE 以及 HDL 级分中的 apoCIII 和 apoE 呈强相关性。调整传统危险因素后，TG、HDL-C、TRL 颗粒浓度、apoCIII 和 apoE 的差异仍然存在。这些结果与精神分裂症患者的 TRL 脂解和清除受损一致，这可能对靶向 apoCIII 有反应。
