Unraveling The Functions Of Macrophage Transporters By Measuring Macrophagespecific Reverse Cholesterol Transport In Vivo

Evaluation of: Wang X, Collins HL, Ranalletta M et al.: Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo. J. Clin. Invest. 117(8), 2216–2224 (2007). Although the role of ATP-binding cassette (ABC)A1, ABCG1 and scavenger receptor class B type I (SR-BI) in the first step in the reverse cholesterol transport (RCT) pathway has been studied in detail, little is known about how these genes regulate cholesterol efflux through the entire pathway. The recent article by Wang et al. quantitatively assessed the relative importance of these molecules in macrophage-specific RCT in vivo. The intraperitoneal injection of [3H]cholesterol-labeled primary ABCA1-deficient macrophages in C57BL/6 mice resulted in reduced RCT from macrophages to feces. By contrast, the injection of primary SR-BI-deficient macrophages did not contribute to this specific RCT pathway. A direct relationship was observed between ABCG1 gene dose and macrophage-specific RCT. Finally, the injection of double ABCA1/ABCG1-knockdown macrophages had additive effects on macrophage-specific RCT, thus emphasizing the critical importance of ABCA1 and ABCG1 in macrophage-specific RCT. Upregulation of these macrophage transporters appears to be, therefore, a desirable target for the development of novel therapies intended to reduce atherosclerosis.