P2Y13 Receptor Regulates HDL Metabolism and Atherosclerosis In Vivo
Figure 1
Increase of HDL recycling following activation of P2Y13R pathway in mice.
C57Bl/6J mice (n = 10) were fasted for 2 h followed by single oral dose of P2Y13R agonist CT1007900 at 3, 30 or 300 µg/kg. Six hours later bile acid content (panel A) and bile cholesterol content (panel B) were evaluated using enzymatic kits. Grey bars represent the amount of bile acid or bile cholesterol per mouse; black bars represent the concentrations of bile acid and bile cholesterol into gallbladder. Panel C, the kinetic of bile acid mobilization in gallbladder induced by CT1007900 at 300 µg/kg (???) by oral gavage (single dosing) using C57Bl/6J mice (n = 5) was evaluated and compared to vehicle treated animals (○). *p<0.05, **p<0.01, ***p<0.0005. Bile acid content of liver (panel D) was evaluated using enzymatic kit. * p<0.05, **p<0.01. Plasma cholesterol (panel E) and plasma apoA-I (panel F) concentrations were determined at different time points after single oral dose of P2Y13R agonist at 100 µg/kg () and compared to vehicle treated animals (○). Values in pre-dose groups for plasma cholesterol vary from 0.85 to 0.95 g/L, and 1.1 to 1.3 g/L for plasma apoA-I. Panel G, C57Bl/6J mice (n = 5) were intravenously injected with [3H]-cholesterol-labelled mouse HDL (10 µCi/mouse) and CT1007900 (10 nmole/kg or 4 µg/kg). Radioactivity present in the liver was determined 2 hours later. **p<0.01. Panel H, C57Bl/6J mice (n = 5) were dosed (single dosing) with CT1007900 (100 µg/kg) and intravenously injected with [3H]-cholesterol-labelled mouse HDL (10 µCi/mouse). Feces from individual mouse were collected for 6 h and extracted for cholesterol (empty bars) and bile acid content (grey bars) and the radioactivity was determined by scintillation counting. *p<0.05.