Institute of Clinical Medicine, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Adv Exp Med Biol. 2022;1377:95-107. doi: 10.1007/978-981-19-1592-5_7.
Cholesterol is a major component of mammalian cell membranes and plays important structural and functional roles. However, excessive cholesterol accumulation is toxic to cells and constitutes the molecular basis for many diseases, especially atherosclerotic cardiovascular disease. Thus, cellular cholesterol is tightly regulated to maintain a homeostasis. Reverse cholesterol transport (RCT) is thought to be one primary pathway to eliminate excessive cholesterol from the body. The first and rate-limiting step of RCT is ATP-binding cassette (ABC) transports A1 (ABCA1)- and ABCG1-dependent cholesterol efflux. In the process, ABCA1 mediates initial transport of cellular cholesterol to apolipoprotein A-I (apoA-I) for forming nascent high-density lipoprotein (HDL) particles, and ABCG1 facilitates subsequent continued cholesterol efflux to HDL for further maturation. In this chapter, we summarize the roles of ABCA1 and ABCG1 in maintaining cellular cholesterol homoeostasis and discuss the underlying mechanisms by which they mediate cholesterol export.
胆固醇是哺乳动物细胞膜的主要成分，发挥着重要的结构和功能作用。然而，过量的胆固醇积累对细胞是有毒的，构成了许多疾病的分子基础，特别是动脉粥样硬化性心血管疾病。因此，细胞胆固醇受到严格调控以维持体内平衡。胆固醇逆转运（RCT）被认为是从体内清除过量胆固醇的主要途径之一。RCT 的第一步和限速步骤是 ATP 结合盒（ABC）转运蛋白 A1（ABCA1）和 ABCG1 依赖性胆固醇外排。在此过程中，ABCA1 将细胞胆固醇最初转运到载脂蛋白 A-I（apoA-I）以形成新生高密度脂蛋白（HDL）颗粒，ABCG1 促进随后的胆固醇继续外排到 HDL 以进一步成熟。在本章中，我们总结了 ABCA1 和 ABCG1 在维持细胞胆固醇平衡中的作用，并讨论了它们介导胆固醇外排的潜在机制。
