Background : Neointima formation is a characteristic feature of atherosclerosis and post-angioplasty restenosis, in which various soluble factors and mechanical injury stimulate signalling pathways in vascular smooth muscle cells (VSMC), promoting their migration and proliferation, and the eventual formation of the neointima. The transcription factor NF-κ κ κ κ B has been

Glucocorticoids are secreted from the adrenal glands and act as a peripheral effector of the hypothalamicpituitary-adrenal axis, playing an essential role in stress response and homeostatic regulation. In target cells, however, it remains unknown how glucocorticoids finetune the cellular pathways mediating tissue and systemic adaptation. Recently, considerable evidence indicates that adaptation to hypoxic environments is influenced by glucocorticoids and there is cross-talk between hypoxia-dependent signals and glucocorticoidmediated regulation of gene expression. We therefore investigated the interaction between these important stress-responsive pathways, focusing on the glucocorticoid receptor (GR) and hypoxia-inducible transcription factor HIF-1. Here we show that, under hypoxic conditions, HIF-1-dependent gene expression is further upregulated by glucocorticoids via the GR. This up-regulation cannot be substituted by the other steroid receptors and is suggested to result from the interaction between the GR and the transactivation domain of HIF-1␣. Moreover, our results also indicate that the ligand binding domain of the GR is essential for this interaction, and the critical requirement for GR agonists suggests the importance of the ligand-mediated conformational change of the GR. Because these proteins are shown to colocalize in the distinct compartments of the nucleus, we suggest that these stress-responsive transcription factors have intimate communication in close proximity to each other, thereby enabling the fine-tuning of cellular responses for adaptation.

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...