Abstract 11181: Effects of Rosuvastatin and Atorvastatin on Macrophage Reverse Cholesterol Transport in Vivo
Clinical trials have consistently shown that statin reduces the incidence of cardiovascular events. While statins significantly decrease LDL-C, it is controversial whether they increase HDL-C and improve HDL function, which plays an important role in macrophage reverse cholesterol transport (RCT). The aim of the present study was to clarify the effects of rosuvastatin and atorvastatin on in vivo macrophage RCT and their underlying mechanisms.
Method and Results: Male C57BL mice were divided into 3 groups (rosuvastatin, atorvastatin and control groups), and orally administrated 4mg/kg/day rosuvastatin, 8mg/kg/day atorvastatin or 0.5% methylcellulose dissolved in water for 6 weeks under feeding with a 0.5% cholesterol diet. After administration, although there were no changes in plasma HDL-C levels among the groups, plasma from the rosuvastatin group showed a 31.5% increase in the ability to promote ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux from J774 cells ex vivo. Capillary electrophoresis revealed a shift of HDL for pre-beta HDL fraction only in the rosuvastatin group. Furthermore, mice in all three groups were intraperitoneally injected with 3H-cholesterol-labeled and cholesterol-loaded macrophages, and then monitored for the appearance of 3H-tracer in plasma and feces. The amount of 3H-tracer excreted into feces over 48 hours in the rosuvastatin group was 45.4% higher than that in the control group, while there were no differences between the atorvastatin and control groups. Finally, 3H-CEs-HDL was intravenously injected into all groups, blood samples were taken and the count of 3H-cholesterol was then analyzed. The plasma 3H-CEs-HDL changed similarly and no differences were observed in fractional catabolic rates among the three groups.
Conclusion We have demonstrated that rosuvastatin activates ABCA1-dependent efflux ex vivo and promotes macrophage RCT in vivo compared with atorvastatin, although there were no changes in plasma HDL-C levels. These data suggest that rosuvastatin, which is a hydrophilic statin, upregulates the HDL-efflux function of RCT, and this finding might help to highlight the potential of rosuvastatin for the regression of atherosclerosis and reduction of cardiovascular disease.
- © 2011 by American Heart Association, Inc.