Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 159, Issue -, Pages 54-93Publisher
ELSEVIER
DOI: 10.1016/j.addr.2020.04.013
Keywords
High density lipoprotein; Atherosclerosis; Diabetes; Reverse cholesterol transport
Categories
Funding
- National University of Singapore
- Agency for Science, Technology and Research (A*STAR), Singapore
- Yong Loo Lin School ofMedicine
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Lipids are hydrophobic and amphiphilic molecules involved in diverse functions such as membrane structure, energy metabolism, immunity, and signaling. However, altered intra-cellular lipid levels or composition can lead to metabolic and inflammatory dysfunction, as well as lipotoxicity. Thus, intra-cellular lipid homeostasis is tightly regulated by multiple mechanisms. Since most peripheral cells do not catabolize cholesterol, efflux (extra-cellular transport) of cholesterol is vital for lipid homeostasis. Defective efflux contributes to atherosclerotic plaque development, impaired beta-cell insulin secretion, and neuropathology. Of these, defective lipid efflux in macrophages in the arterial walls leading to foam cell and atherosclerotic plaque formation has been the most well studied, likely because a leading global cause of death is cardiovascular disease. Circulating high density lipoprotein particles play critical roles as acceptors of effluxed cellular lipids, suggesting their importance in disease etiology. We review here mechanisms and pathways that modulate lipid efflux, the role of lipid efflux in disease etiology, and therapeutic options aimed at modulating this critical process. (C) 2020 Elsevier B.V. All rights reserved.
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