Nicotinic acid improves reverse cholesterol transport in dogs

Abstract

Nicotinic acid (NA) improves plasma lipids but the involved mechanisms have not been fully elucidated. A higher HDL‐cholesterol (HDL‐C) concentration has been observed in humans, and the role of cholesteryl ester transfer protein (CETP) in this raise remains to be determined. With this aim, we assessed the NA effect on the reverse cholesterol transport (RCT) in the dog, which is a CETP‐devoid species. RCT was assessed through stable isotope endogenous labeling of HDL‐C and apoAI moieties. NA treatment lowered triglyceride (TG) plasma concentration (p < 0.01) due to a diminution in VLDL‐TG (p < 0.05). Cholesterol plasma concentration was reduced (p < 0.0001) as a result of lowered concentration of both LDL‐C (p < 0.05) and HDL‐C (p < 0.0001). Kinetic studies showed a higher cholesterol esterification rate (p < 0.05) that was in accordance with a rise in cholesterol efflux as measured in vitro (p < 0.05). Cholesterol turnover was accelerated via selective uptake of both HDL and cholesterol esters that explain the HDL‐C reduction (p < 0.05 for both). In conclusion, this study shows that, in CETP‐devoid species as dogs, NA would lower HDL due to a higher catabolism, which would reflect a more active RCT. Moreover, in humans or in other CETP species, NA could also raise HDL‐C as a result of a reduction in plasma TG. Since it has been shown a higher HDL‐C concentration after NA treatment, this second effect should be predominant in human.