INSERM U1060, Carmen laboratory, INSA de Lyon, Villeurbanne, France (C.L.-C.).
ANZAC Research institute, Concord Repatriation General Hospital and University of Sydney, Australia (M.K., M.A., V.C., W.J., L.K.).
Arterioscler Thromb Vasc Biol. 2020 Nov;40(11):2728-2737. doi: 10.1161/ATVBAHA.120.314847. Epub 2020 Sep 10.
Patients with schizophrenia have increased long-term mortality attributable to cardiovascular disease and commonly demonstrate features of mixed dyslipidemia with low HDL-C (high-density lipoprotein cholesterol). The removal of cholesterol from cells by HDL via specific ATP-binding cholesterol transporters is a major functional property of HDL, and its measurement as cholesterol efflux capacity (CEC) can predict cardiovascular risk. Whether HDL function is impaired in patients with schizophrenia is unknown. Approach and Results: We measured basal and ABCA1 (ATP-binding cassette transporter A1)- and ABCG1 (ATP-binding cassette transporter G1)-dependent CEC, comparing patients with schizophrenia with age- and sex-matched healthy controls, and related our findings to nuclear magnetic resonance analysis of lipoprotein subclasses. Total plasma cholesterol and LDL-C (low-density lipoprotein cholesterol) were comparable between healthy controls (n=51) and patients (n=120), but patients with schizophrenia had increased total plasma triglyceride, low HDL-C and apo (apolipoprotein) A-I concentrations. Nuclear magnetic resonance analysis indicated a marked (15-fold) increase in large triglyceride-rich lipoprotein particle concentration, increased small dense LDL particles, and fewer large HDL particles. Despite lower HDL-C concentration, basal CEC was 13.7±1.6% higher, ABCA1-specific efflux was 35.9±1.6% higher, and ABCG1 efflux not different, in patients versus controls. In patients with schizophrenia, ABCA1-specific efflux correlated with the abundance of small 7.8 nm HDL particles but not with serum plasminogen or triglyceride levels.
Patients with schizophrenia have increased concentrations of atherogenic apoB-containing lipoproteins, decreased concentrations of large HDL particles, but enhanced ABCA1-mediated CEC. In this population, preventative strategies should focus on reducing atherogenic lipoproteins rather than increasing CEC.
精神分裂症患者的心血管疾病长期死亡率增加，且常表现出混合性血脂异常，伴有低 HDL-C（高密度脂蛋白胆固醇）。HDL 通过特定的 ATP 结合胆固醇转运蛋白将胆固醇从细胞中清除，这是 HDL 的主要功能特性，其胆固醇外排能力（CEC）的测量可预测心血管风险。精神分裂症患者的 HDL 功能是否受损尚不清楚。方法和结果：我们测量了基础状态以及 ABCA1（ATP 结合盒转运蛋白 A1）和 ABCG1（ATP 结合盒转运蛋白 G1）依赖性 CEC，比较了精神分裂症患者和年龄、性别匹配的健康对照者，并将我们的发现与脂蛋白亚类的核磁共振分析相关联。健康对照组（n=51）和精神分裂症患者（n=120）的总血浆胆固醇和 LDL-C（低密度脂蛋白胆固醇）相当，但精神分裂症患者的总血浆甘油三酯、低 HDL-C 和载脂蛋白 A-I 浓度升高。核磁共振分析表明，大的富含甘油三酯的脂蛋白颗粒浓度显著增加（增加了 15 倍），小而密的 LDL 颗粒增加，大的 HDL 颗粒减少。尽管 HDL-C 浓度较低，但与对照组相比，基础 CEC 高 13.7±1.6%，ABCA1 特异性外排高 35.9±1.6%，ABCG1 外排无差异。在精神分裂症患者中，ABCA1 特异性外排与 7.8nm 小 HDL 颗粒的丰度相关，而与血清纤溶酶原或甘油三酯水平无关。结论：精神分裂症患者的载脂蛋白 B 含脂蛋白浓度增加，大的 HDL 颗粒浓度降低，但 ABCA1 介导的 CEC 增强。在该人群中，预防策略应侧重于减少致动脉粥样硬化的脂蛋白，而不是增加 CEC。
