Parameters evaluated
- Plasma total cholesterol, HDL-c and HDL-c/TC ratio
- ³H-cholesterol appearance from macrophage to plasma and liver
- Macrophage-derived cholesterol fecal excretion: ³H-tracer recovered in fecal free sterols and bile acids
State-of-the-art technique to directly demonstrate that your compound promotes reverse cholesterol transport and has therefore the potential to prevent cardiovascular diseases.
In vivo reverse cholesterol transport using radiolabeled cholesterol is the best approach to evaluate compounds affecting HDL metabolism and reverse cholesterol transport.
Species : hamster - mouse - rat
Scientific and pharmacological relevance
- Hamsters fed a chow + 0.3% cholesterol diet over 4 weeks then treated with vehicle or LXR agonist GW3965
- Treatment: LXR agonist GW3965 30mg/kg, twice daily
- Duration: 10 days
LXR activation promotes macrophage-to-feces in vivo reverse cholesterol transport in hamsters fed a chow +0.3% cholesterol diet :
- 30% increase in 3H-cholesterol plasma appearance after radiolabeled macrophages injection
- 3H-tracer recovery in liver increases by 27%, 72h after radiolabeled macrophages injection
- macrophage-derived cholesterol fecal excretion (as free sterols) increases by 156%, 72h after radiolabeled macrophages injection
Key benefits
- Demonstrate a beneficial effects of your compound on macrophage-to-feces reverse cholesterol transport
- Essential and robust data to demonstrate that your compound promotes the transport of cholesterol from peripheral tissues to the feces and has therefore the potential to prevent atherosclerosis
Add on studies
- HDL-cholesterol turn over
- Biochemical analysis: plasma lipids, HDL-c, lipoprotein profiles, transfer protein activity assays (CETP, PLTP), ect...
References and publications
Castro-Perez J, Briand F, Gagen K, Wang SP, Chen Y, McLaren DG, Shah V,
Vreeken RJ, Hankemeier T, Sulpice T, Roddy TP, Hubbard BK, Johns DG.
Anacetrapib promotes reverse cholesterol transport and bulk cholesterol excretion in Syrian golden hamsters.
J Lipid Res. 2011 Nov;52(11):1965-73.
Nijstad N, Gautier T, Briand F, Rader DJ, Tietge UJ.
Biliary sterol secretion is required for functional in vivo reverse cholesterol transport in mice.
Gastroenterology. 2011 Mar;140(3):1043-51.
Tréguier M, Briand F, Boubacar A, André A, Magot T, Nguyen P, Krempf M, Sulpice T, Ouguerram K.
Diet-induced dyslipidemia impairs reverse cholesterol transport in hamsters.
Eur J Clin Invest. 2011 Sep;41(9):921-8.
Fabre AC, Malaval C, Ben Addi A, Verdier C, Pons V, Serhan N, Lichtenstein
L, Combes G, Huby T,Briand F, Collet X, Nijstad N, Tietge UJ, Robaye B,
Perret B, Boeynaems JM, Martinez LO.
P2Y13 receptor is critical for reverse cholesterol transport.
Hepatology. 2010 Oct;52(4):1477-83.
Briand F, Tréguier M, André A, Grillot D, Issandou M, Ouguerram K, Sulpice T.
Liver X receptor activation promotes macrophage-to-feces reverse cholesterol transport in a dyslipidemic hamster model.
J Lipid Res. 2010 Apr;51(4):763-70.
Briand F.
The use of dyslipidemic hamsters to evaluate drug-induced
alterations in reverse cholesterol transport.
Curr Opin Investig Drugs. 2010 Mar;11(3):289-97.
Briand F, Naik SU, Fuki I, Millar JS, Macphee C, Walker M, Billheimer J, Rothblat G, Rader DJ.
Both the Peroxisome Proliferator-Activated Receptor Agonist, GW0742, and Ezetimibe Promote Reverse Cholesterol Transport in Mice by Reducing Intestinal Reabsorption of HDL-Derived Cholesterol.
Clin trans Sci. 2009; 2:127-133.
Briand F, Burcelin R, Sulpice T.
DPP-4 Inhibitor sitagliptin improves reverse cholesterol transport through reduced intestinal cholesterol absorption in obese insulin resistant CETP-apoB100 transgenic mice.
American Diabetes Association , June 24-28, 2011, San Diego, California,
USA.