Diet-induced dyslipidemia impairs reverse cholesterol transport in hamsters

作者：Treguier Morgan; Briand Francois; Boubacar Adamou; Andre Agnes; Magot Thierry; Nguyen Patrick; Krempf Michel; Sulpice Thierry; Ouguerram Khadija^*

来源：European Journal of Clinical Investigation, 2011, 41(9): 921-928.

DOI：10.1111/j.1365-2362.2011.02478.x

• Atherosclerosis
• dyslipidemia
• hamster
• macrophage
• reverse cholesterol transport

Background Reverse cholesterol transport (RCT) is an anti-atherogenic process by which cholesterol is effluxed from peripheral tissues by high-density lipoprotein (HDL) and returned to the liver for excretion into the bile and faeces. Dyslipidemia is thought to impair RCT through higher triglyceride-rich lipoprotein (TRL), low HDL-cholesterol and higher activity of cholesteryl ester transfer protein (CETP), which transfers cholesteryl esters from HDL to TRL for further hepatic uptake. As CETP pathway would represent a major route in human RCT, we therefore investigated whether diet-induced dyslipidemia impairs RCT in hamster, a CETP-expressing species.
Materials and methods Golden Syrian hamsters were fed a chow or chow+0.3% cholesterol diet over 4 weeks. Biochemical parameters and in vivo VLDL-triglycerides secretion (Triton WR-1339 injection) were then measured. In vitro macrophage cholesterol efflux was measured, and in vivo macrophage-to-faeces RCT was also assessed after an intraperitoneal injection of (3)H-cholesterol-labelled hamster primary macrophages.
Results Cholesterol-enriched diet increased plasma total cholesterol (144%), triglycerides (101%), VLDL-triglycerides secretion (175%), CETP activity (44%) and reduced HDL-cholesterol/total cholesterol ratio by 20% (P < 0.01 vs. chow). Cholesterol-enriched diet significantly increased hepatic total cholesterol and triglycerides by 459 and 118% and increased aortic total cholesterol content by 304%. In vitro cholesterol efflux from macrophages to plasma was significantly reduced by 25% with plasma from cholesterol-fed hamsters. In vivo RCT experiments showed a significant 75% reduction of macrophage-derived cholesterol faecal excretion in cholesterol-fed hamsters.
Conclusions Overall, these data demonstrate that diet-induced dyslipidemia severely impairs in vivo RCT in hamsters.

• 出版日期2011-9