来自1型糖尿病患者的血促进了人类巨细胞中益动质胆固醇的运输
Siham Accacha1, Iryna Voloshyna2, Lora J Kasselman3
1Department of Pediatrics, NYU Langone Hospital Long Island, Mineola, NY, USA.
概括
患有1型糖尿病的青少年的血通过破坏巨细胞中的胆固醇平衡来加速动脉样硬化,通过先进的糖化终产物增加脂质积累和泡细胞形成.
科学领域:
- 心血管研究研究心血管研究
- 内分泌学 在内分泌学.
- 代谢综合征是代谢综合征的一种.
背景情况:
- 1型糖尿病 (T1DM) 中的高血糖会通过先进的糖化终产物 (AGEs) 加快动脉样硬化.
- 通过降低ATP结合膜带输送器A1和G1 (ABCA1和ABCG1) 的下调,AGE会损害逆胆固醇输送 (RCT).
- 巨细胞中胆固醇稳态的破坏是糖尿病血管并发症的关键因素.
研究的目的:
- 为了研究青少年的血是否控制不良的T1DM扰乱胆固醇在人类单细胞/巨细胞的恒常性.
- 评估T1DM血对胆固醇外流和巨细胞吸收途径的影响.
- 为了证实T1DM血对巨细胞泡细胞形成的亲有氧效应.
主要方法:
- 从20名健康对照组 (HCs) 和20名患有T1DM的青少年 (10-19岁) 收集了血.
- 从HC和T1DM患者的血中暴露原始的THP-1巨细胞.
- 胆固醇运输基因 (ABCA1,ABCG1,27-基酶,CD36,SCR-A1,LOX-1,CXCL16) 的量化mRNA表达和泡细胞的形成.
主要成果:
- 在T1DM血中,N- ((carboxymethyl) -lysine修饰蛋白的含量升高,CXCL16和ScR-A1mRNA的调节升高.
- 暴露于T1DM等离子体导致TPH-1巨细胞中的脂质积累增加和泡细胞形成.
- 巨细胞对AGE的吸收主要通过SR-A1和CXCL16受体发生,增加细胞内氧化低密度脂蛋白.
结论:
- 患有T1DM的青少年的血破坏了巨细胞胆固醇稳态.
- 通过影响胆固醇吸收和排放,AGE有助于T1DM中的加速动脉样硬化.
- 准AGE和胆固醇运输通路可能会减轻糖尿病心血管并发症.
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