VLDL/LDL acts as a drug carrier and regulates the transport and metabolism of drugs in the body.
VLDL/LDL acts as a drug carrier and regulates the transport and metabolism of drugs in the body.
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DOI：
10.1038/s41598-017-00685-9
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发表时间：
2017-04-04
影响因子：
4.6
通讯作者：
Suzuki H
中科院分区：
文献类型：
--
作者：
Yamamoto H;Takada T;Yamanashi Y;Ogura M;Masuo Y;Harada-Shiba M;Suzuki H
只有游离药物被认为是通过主动或被动转运进入组织的。然而，考虑到脂蛋白作为血清脂质（如胆固醇和甘油三酯）的载体，我们假设脂蛋白可以与某些药物结合，并以脂质结合形式介导其转运到组织中。在这里，在体外和体内研究低密度脂蛋白受体（LDLR）过表达或敲低细胞和野生型或LDLR突变小鼠被用来显示各种药物与脂蛋白和脂蛋白相关药物的摄取通过脂蛋白受体介导的过程的协会。在临床研究中，研究了脂蛋白单采术对家族性高胆固醇血症患者血清药物浓度的影响，结果表明，人和小鼠均存在脂蛋白介导的药物转运。这些研究结果代表了一个新的概念，关于运输和代谢的药物在体内，并建议脂蛋白介导的药物运输的作用时，应考虑开发有效和安全的药物治疗。
Only free drugs have been believed to be carried into tissues through active or passive transport. However, considering that lipoproteins function as carriers of serum lipids such as cholesterol and triglycerides, we hypothesized that lipoproteins can associate with certain drugs and mediate their transport into tissues in lipid-associated form. Here, in vitro and in vivo studies with low density lipoprotein receptor (LDLR)-overexpressing or -knockdown cells and wild-type or LDLR-mutant mice were used to show the association of various drugs with lipoproteins and the uptake of lipoprotein-associated drugs through a lipoprotein receptor-mediated process. In clinical studies, investigation of the effect of lipoprotein apheresis on serum drug concentrations in patients with familial hypercholesterolemia demonstrated that lipoprotein-mediated drug transport occurs in humans as well as in mice. These findings represent a new concept regarding the transport and metabolism of drugs in the body and suggest that the role of lipoprotein-mediated drug transport should be considered when developing effective and safe pharmacotherapies.