Department of Analytical Laboratory Chemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Baker Heart and Diabetes Institute, Melbourne, Australia.
Baker Heart and Diabetes Institute, Melbourne, Australia.
J Lipid Res. 2020 Dec;61(12):1577-1588. doi: 10.1194/jlr.RA120000635. Epub 2020 Sep 9.
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 and 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.
脂蛋白在胆固醇向组织和从组织的运输中起着关键作用。最近的研究还表明，红细胞（RBC）在其膜中携带大量游离胆固醇，在胆固醇逆向转运中起着重要作用。然而，RBC 在全身胆固醇代谢中的确切作用仍不清楚。将 RBC 与自体血浆或分离的脂蛋白孵育，导致大量胆固醇从 RBC 转移到 HDL，而 LDL 中的胆固醇则向相反方向移动。此外，RBC 与血浆脂蛋白之间的双向胆固醇转运是饱和的，且依赖于温度、能量和时间，这与主动过程一致。我们在 RBC 中未发现 LDLR、ABCG1 或清道夫受体 B 类 1，但发现了大量的 ABCA1 mRNA 和蛋白。然而，RBC 特异性向分离的 apoA-I 中排出的胆固醇可以忽略不计，并且用 siRNA 沉默 ABCA1 或用钒酸盐和丙丁酚抑制，均不能抑制 apoA-I、HDL 或血浆的流出。和 小鼠的 RBC 从胆固醇的排出和摄取相似，这表明 ABCA1 不可能在 RBC 与脂蛋白之间的胆固醇通量中起作用。生物信息学分析确定 ABCA7、ABCG5、脂蛋白脂肪酶和线粒体转位蛋白可能是介导胆固醇通量的候选物。总之，这些结果表明 RBC 积极参与血液中的胆固醇运输，但胆固醇转运蛋白在 RBC 中的作用仍不确定。
