Increased ABCA1 (ATP-Binding Cassette Transporter A1)-Specific Cholesterol Efflux Capacity in Schizophrenia
Increased ABCA1 (ATP-Binding Cassette Transporter A1)-Specific Cholesterol Efflux Capacity in Schizophrenia
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DOI：
10.1161/atvbaha.120.314847
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发表时间：
2020-11-01
影响因子：
8.7
通讯作者：
Kritharides, Leonard
中科院分区：
文献类型：
--
作者：
Luquain-Costaz, Celine;Kockx, Maaike;Kritharides, Leonard
目的：精神分裂症患者因心血管疾病导致的长期死亡率增加，常表现为混合性血脂异常和低高密度脂蛋白胆固醇(HDLC)。高密度脂蛋白通过特定的三磷酸腺苷结合的胆固醇转运体从细胞中清除胆固醇是高密度脂蛋白的一个主要功能特性，其测量的胆固醇流出能力(CEC)可以预测心血管风险。方法与结果：我们测量了基础和ABCA1(ATP结合盒转运体A1)和Abcg1(ATP结合盒转运体G1)依赖的CEC，将精神分裂症患者与年龄和性别匹配的健康对照组进行比较，并将我们的发现与脂蛋白亚类的核磁共振分析相关联。正常对照组(n=51)和精神分裂症患者(n=120)的血浆总胆固醇和低密度脂蛋白胆固醇水平相近，但精神分裂症患者血浆总甘油三酯升高，低密度脂蛋白胆固醇和载脂蛋白A-I浓度降低。核磁共振分析表明，富含甘油三酯的大颗粒脂蛋白浓度显著增加(15倍)，小而致密的低密度脂蛋白颗粒增加，大的高密度脂蛋白颗粒减少。尽管HDLC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特异性外流与7.8 nm小颗粒高密度脂蛋白的丰度相关，而与血清纤溶酶原或甘油三酯水平无关。结论：精神分裂症患者动脉粥样硬化相关载脂蛋白B浓度升高，大颗粒高密度脂蛋白浓度降低，ABCA1介导的CEC升高。在这一人群中，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。
Objective: 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.Conclusions: 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.Graphic Abstract: A is available for this article.