Cholesterol transport between red blood cells and lipoproteins contributes to cholesterol metabolism in blood
Cholesterol transport between red blood cells and lipoproteins contributes to cholesterol metabolism in blood
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DOI：
10.1194/jlr.ra120000635
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发表时间：
2020-12-01
影响因子：
6.5
通讯作者：
Tozuka, Minoru
中科院分区：
文献类型：
--
作者：
Ohkawa, Ryunosuke;Low, Hann;Tozuka, Minoru
脂蛋白在胆固醇进出组织的运输中起着关键作用。最近的研究还表明，红细胞（rbc）在其膜上携带大量的游离胆固醇，在逆向胆固醇运输中发挥重要作用。然而，红细胞在全身胆固醇代谢中的确切作用尚不清楚。红细胞与自体血浆或分离的脂蛋白孵育，导致大量胆固醇从红细胞转移到HDL，而LDL的胆固醇向相反方向移动。此外，红细胞和血浆脂蛋白之间的双向胆固醇转运是饱和的，并且依赖于温度、能量和时间，与一个主动过程相一致。我们没有在红细胞中发现LDLR、ABCG1或B型1清除率受体，但发现了大量的ABCA1 mRNA和蛋白。然而，从红细胞到分离的apoA-I的特异性胆固醇外排可以忽略不计，用siRNA沉默ABCA1或用钒酸盐和普罗布考抑制ABCA1并不能抑制apoA-I、HDL或血浆的外排。Abca1（+/+）和Abca1（-/-）小鼠红细胞的胆固醇外排和胆固醇摄取相似，反驳了Abca1在红细胞和脂蛋白之间胆固醇流动中的作用。生物信息学分析发现ABCA7、ABCG5、脂蛋白脂肪酶和线粒体转运蛋白可能是介导胆固醇流动的候选物质。总之，这些结果表明红细胞积极参与血液中的胆固醇运输，但胆固醇转运体在红细胞中的作用仍不确定。
Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBCs to HDL, while cholesterol from LDL moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBCs and plasma lipoproteins was saturable and temperature-, energy-, and time-dependent, consistent with an active process. We did not find LDLR, ABCG1, or scavenger receptor class B type 1 in RBCs but found a substantial amount of ABCA1 mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apoA-I was negligible, and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL, or plasma. Cholesterol efflux from and cholesterol uptake by RBCs from Abca1(+/+) and Abca1(-/-) mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBCs and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, lipoprotein lipase, and mitochondrial translocator protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBCs remains uncertain.