Current models of apolipoprotein A-I lipidation by adenosine triphosphate binding cassette transporter A1. Curr Opin Lipidol 2022 Apr 01;33(2):139-145
Date
09/29/2021Pubmed ID
34581311DOI
10.1097/MOL.0000000000000786Scopus ID
2-s2.0-85125682549 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
PURPOSE OF REVIEW: The primary cardioprotective function of high-density lipoprotein (HDL) is to remove excess cellular free cholesterol (FC) from peripheral tissues and deliver it to the liver. Here, we summarize recent research that examines apolipoprotein A-I (apoA-I) lipidation models by adenosine triphosphate binding cassette transporter A1 (ABCA1) and discuss its relevance in atherosclerotic cardiovascular disease (ASCVD).
RECENT FINDINGS: The first step in HDL formation involves the interaction between apoA-I and ABCA1, where ABCA1 mediates the removal of FC and phospholipids from lipid-laden macrophages to form discoidal nascent HDL (nHDL). However, there are currently no clear-cut systematic models that characterize HDL formation. A number of recent studies have investigated the importance of apoA-I C- and N-terminal domains required for optimal cholesterol efflux and nHDL production. Furthermore, functional ABCA1 is required for direct or indirect binding to apoA-I where ABCA1 dimer-monomer interconversion facilitates apoA-I lipidation from plasma membrane microdomains. Microparticles are also another lipid source for apoA-I solubilization into nHDL.
SUMMARY: ApoA-I and ABCA1 are key factors in macrophage-mediated cholesterol efflux and nHDL production. Understanding of the key steps in HDL formation may unlock the therapeutic potential of HDL and improve clinical management of ASCVD.
Author List
Hafiane A, Gianopoulos I, Sorci-Thomas MG, Daskalopoulou SSAuthor
Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ATP Binding Cassette Transporter 1Apolipoprotein A-I
Atherosclerosis
Cholesterol
Humans
Lipoproteins, HDL
