P2Y13 Receptor Regulates HDL Metabolism and Atherosclerosis In Vivo
Figure 2
Repeated dosing of P2Y13R agonist decreases HDL-C.
Plasma cholesterol (panel A), plasma apoA-I (panel B) and plasma lipoproteins (panel C) concentrations were determined after 2 weeks oral dose of P2Y13R agonist at 100 µg/kg (grey bars) and compared to vehicle treated animals (empty bars). Values for plasma apoA-I vary from 1.5 to 1.85 g/L. *p<0.05. Panel D, Concentration of liver apoA-I was determined by Western-blot quantification (n = 4 mouse/group) using imageJ software. 40 µg of total liver extract (vehicle or CT1007900 at 100 µg/kg) were separated on the same 12.5% SDS-PAGE and probed with goat anti-apoA-I antibody. *p<0.05. Panel E, the ratios of apoA-I/plasma cholesterol concentrations were determined and compared to their respective pre-dose values. Panel F, HDL from C57Bl/6J mouse plasma were separated according to the size of the different HDL particles using the Lipoprint system. The data were expressed as the percentage of difference for each HDL subpopulation set to the HDL population in the pre-dose animals. **p<0.01. Panel G, Determination of cholesterol efflux capacity of mouse plasma (1% v/v) using pre-loaded [3H]-cholesterol-oxLDL macrophages. The results are expressed as a percentage of cholesterol efflux corrected from pre-dose. Values for cholesterol efflux before correction from pre-dose vary from 12–15%. *p<0.05.