A novel model of cholesterol efflux from lipid-loaded cells

Abstract

Cholesterol efflux from lipid-loaded cells is a key athero-protective event that counteracts cholesterol uptake. The imbalance between cholesterol efflux and uptake determines the prevention or development of atherosclerosis. Many proteins and factors participate in the cholesterol efflux event. However, there are currently no systematic models of reverse cholesterol transport (RCT) that include most RCT-related factors and events. On the basis of recent research findings from other and our laboratories, we propose a novel model of one center and four systems with coupling transportation and networking regulation. This model represents a common way of cholesterol efflux; however, the systems in the model consist of different proteins/factors in different cells. In this review, we evaluate the novel model in vascular smooth muscle cells (VSMCs) and macrophages, which are the most important original cells of foam cells. This novel model consists of 1) a caveolae transport center, 2) an intracellular trafficking system of the caveolin-1 complex, 3) a transmembrane transport system of the ABC-A1 complex, 4) a transmembrane transport system of the SR-B1 complex, and 5) an extracelluar trafficking system of HDL/Apo-A1. In brief, the caveolin-1 system transports cholesterol from intracellular compartments to caveolae. Subsequently, both ABC-A1 and SR-B1 complex systems transfer cholesterol from caveolae to extracellular HDL/Apo-A1. The four systems are linked by a regulatory network. This model provides a simple and concise way to understand the dynamic process of atherosclerosis.

Dietary Ellagic Acid Attenuates Oxidized LDL Uptake and Stimulates Cholesterol Efflux in Murine Macrophages3

“…Cholesterol efflux is regulated by stimulation of ABCA1 and ABGA1 (11,12,31). Membrane SR-B1 is also involved in transferring cholesterol to extracellular HDL/apoA1 and influences reverse cholesterol transport, indicating a dual role of SR-B1 in cholesterol trafficking (32). In this study, the late SR-B1 induction was not involved in the ellagic acid-promoted cholesterol efflux from lipid-laden foam cells.…”

ABCA1 overexpression worsens colorectal cancer prognosis by facilitating tumour growth and caveolin‐1‐dependent invasiveness, and these effects can be ameliorated using the BET inhibitor apabetalone

“…Caveolae were proposed to be part of the complex regulating cholesterol efflux and to be the principal location at which plasma membrane cholesterol is exchanged between HDL and cells membrane (Luo et al ., ; Qin et al ., ). Increased transcription of ABCA1 was associated with CAV‐1 stabilization in prostate cancer‐derived cells (Cohen et al ., ; Her et al ., ).…”

Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

“…However, previous cholesterol disorder studies focused on the serum or macrophages, and information on tissues under diabetic states has not been fully examined. An important way to maintain cellular cholesterol homeostasis is reverse cholesterol transport (RCT) via cholesterol transporters [8] . ATP-binding cassette protein A1 (ABCA1) is an important rate-controlling protein in reverse cholesterol transport.…”