ABCA1: A Possible Link Between Inflammation And Reverse Cholesterol Transport

Atherosclerosis is characterized by a chronic inflammatory condition, in which numerous cellular and molecular inflammatory components are involved. A wide array of inflammatory mediators, such as cytokines and proteins produced by macrophages and other cells, play critical roles in the development and progression of the disease. ABCA1 is crucial for cellular cholesterol efflux and reverse cholesterol transport (RCT), and also identified as an important target in anti-atherosclerosis treatment. Evidences from many recent studies indicate that inflammation impaired RCT, and many atherogenic-related mediators played distinct regulating roles in ABCA1 expression. Pro-atherogenic cytokines such as interferon gamma (IFN-γ), interleukin-1beta (IL-1β) have been shown to inhibit the expression of ABCA1. However, anti-atherogenic cytokines, including interleukin-10 (IL-10) and transforming growth factor beta1 (TGF-β1), have been described to promote the expression of ABCA1 while some cytokines like as tumor necrosis factor alpha(TNF-α) seem to regulate ABCA expression in species-specific and dose-dependent manners. Furthermore, inflammatory proteins such as C-reactive protein (CRP) and cyclooxygenase 2(COX-2) are likely to inhibit ABCA1 expression during inflammation, and inflammation induced by LPS was also found to block the expression of ABCA1. Interestingly, recent experiments revealed ABCA1 can function as an anti-inflammatory receptor to suppress the expression of inflammatory factors, suggesting that ABCA1 may be the molecular basis for the interaction between inflammation and RCT. This review aims to summarize recent findings on the role of inflammatory cytokines, inflammatory proteins, inflammatory lipids, and endotoxin-mediated inflammatory process in expression of ABCA1. It will also cover current understanding of the function of ABCA1 in modulating the immune and inflammation through its direct and indirect anti-inflammatory mechanisms including lipids transport, HDL formation and apoptosis. Supplementary key words: ATP-binding cassette transporter A1; Inflammation; Cytokine; Atherosclerosis; Reverse cholesterol transport Molecular Medicine www.molmed.org U N C O R R E C TE D P R O O F