Coffee Consumption Enhances High-Density Lipoprotein-Mediated Cholesterol Efflux in Macrophages

Abstract

Rationale: Association of habitual coffee consumption with coronary heart disease morbidity and mortality has not been established. We hypothesized that coffee may enhance reverse cholesterol transport (RCT) as the antiatherogenic properties of high-density lipoprotein (HDL). Objective: This study was to investigate whether the phenolic acids of coffee and coffee regulates RCT from macrophages in vitro, ex vivo and in vivo. Methods and Results: Caffeic acid and ferulic acid, the major phenolic acids of coffee, enhanced cholesterol efflux from THP-1 macrophages mediated by HDL, but not apoA-I. Furthermore, these phenolic acids increased both the mRNA and protein levels of ATP-binding cassette transporter (ABC)G1 and scavenger receptor class B type I (SR-BI), but not ABCA1. Eight healthy volunteers were recruited for the ex vivo study, and blood samples were taken before and 30 minutes after consumption of coffee or water in a crossover study. The mRNA as well as protein levels of ABCG1, SR-BI, and cholesterol efflux by HDL were increased in the macrophages differentiated under autologous sera obtained after coffee consumption compared to baseline sera. Finally, effects of coffee and phenolic acid on in vivo RCT were assessed by intraperitoneally injecting Key Words: HDL cholesterol Ⅲ efflux Ⅲ coffee Ⅲ phenolic acid H igh-density lipoproteins (HDLs) have been shown to be inversely associated with the risk of atherosclerotic cardiovascular disease (CVD) 1,2 and thus considered as antiatherogenic lipoproteins. Among antiatherogenic mechanisms including beneficial effects on inflammation, impaired endothelial function or hypercoagulation, HDL exerts the antiatherogenic property primarily by facilitating the efflux of cholesterol from peripheral tissues and transport it back to the liver in a process called reverse cholesterol transport (RCT). A major breakthrough in the understanding of the mechanism of RCT came with the discovery of the ATP binding cassette transporter (ABC)A1. Lipid-poor apolipoprotein (apo)A-I contributes to ABCA1-mediated cholesterol efflux from cells, but not HDL. 3,4 Another ABC transporter, ABCG1, is also involved in the cholesterol efflux from macrophages mediated by HDL, but not apoA-I. 4,5 Scavenger receptor class B type I (SR-BI) is also known to promote HDL-mediated cellular cholesterol efflux. 6 Furthermore, the pivotal roles of these molecules on intracellular cholesterol homeostasis, associated with reverse cholesterol transport, have also been confirmed by animal studies where deletions of ABCA1, 7 ABCG1, 8 and SR-BI 9 in macrophages accelerated the development of atherosclerosis.Coffee is among the most widely consumed beverages worldwide. The relationship between coffee consumption and the incidence of CVD has been studied extensively. 10 -12 In addition, a recent study reported that regular coffee consumption might be associated with a decreased cardiovascular mortality rate. 13 Coffee beans are known to be abundant in antioxidant phenolic acids, chlorogenic acid. Indeed, Xia M et...

Astaxanthin Enhances ATP-Binding Cassette Transporter A1/G1 Expressions and Cholesterol Efflux from Macrophages

“…Anthocyanins, a large group of naturally phe-nolic compounds abundant in plants, enhanced ABCA1 expression by stimulating PPAR ␥ /LXR pathways, thus resulting in increased cholesterol efflux from macrophages. We recently observed that coffee's phenolic acids, caffeic/ferulic acids, induced ABCG1 and scavenger receptor class B, type I (SR-BI) expression, which is also involved in HDL-mediated cholesterol efflux, leading to increased HDL-mediated cholesterol efflux from macrophages ( 8 ). Additionally, in line with the in vitro finding, ferulic acid was found to promote overall RCT in vivo in mice.…”

Effect of Sulfonylurea Agents on Reverse Cholesterol Transport in Vitro and Vivo

“…3 Hcholesterol-labeled and acLDL-loaded RAW264.7 cells (typically 5.0 10 6 cells containing 7.5 10 6 counts per minute [cpm] in 0.5 mL RPMI 1640) were injected intraperitoneally as described previously [21][22][23] . Blood samples were obtained from the tail vein under anesthesia prior to administration of the SUAs and at 24 and 48 h after injection of RAW264.7 cells.…”

“…Liver lipids were extracted as described previously [21][22][23] . Briefly, a 50 mg piece of tissue was homogenized in water, and lipids were extracted with a 2:1 (vol/vol) mixture of chloroform/methanol.…”

Sage weed (Salvia plebeia) extract antagonizes foam cell formation and promotes cholesterol efflux in murine macrophages

“…This study failed to show promoting effects of homoplantaginin and hispidulin, on ABCA1 expression. However, caffeic acid, one of Salvia plebeia constituents, enhanced cholesterol efflux from THP-1 macrophages mediated by HDL, and induced expression of ABCG1 and SR-BI but not ABCA1 (26). Thus, other unknown components appeared to be responsibe for increasing cholesterol efflux and HDL formation by SWE.…”