Skip to Main content Skip to Navigation
Journal articles

Chronic pharmacological activation of P2Y13 receptor in mice decreases HDL-cholesterol level by increasing hepatic HDL uptake and bile acid secretion.

Abstract : High level of high-density lipoprotein cholesterol (HDL-cholesterol) is inversely correlated to the risk of atherosclerotic cardiovascular disease. The protective effect of HDL is mostly attributed to their metabolic functions in reverse cholesterol transport (RCT), a process whereby excess cell cholesterol is taken up from peripheral cells and processed in HDL particles, and is later delivered to the liver for further metabolism and bile excretion. We have previously demonstrated that P2Y13 receptor is critical for RCT and that intravenous bolus injection of cangrelor (AR-C69931MX), a partial agonist of P2Y13 receptor, can stimulate hepatic HDL uptake and subsequent lipid biliary secretion without any change in plasma lipid levels. In the present study, we investigated the effect of longer-term treatment with cangrelor on lipoprotein metabolism in mice. We observed that continuous delivery of cangrelor at a rate of 35μg/day/kg body weight for 3days markedly decreased plasma HDL-cholesterol level, by increasing the clearance of HDL particles by the liver. These effects were correlated to an increase in the rate of biliary bile acid secretion. An increased expression of SREBP-regulated genes of cholesterol metabolism was also observed without any change of hepatic lipid levels as compared to non-treated mice. Thus, 3-day cangrelor treatment markedly increases the flux of HDL-cholesterol from the plasma to the liver for bile acid secretion. Taken together our results suggest that P2Y13 appears a promising target for therapeutic intervention aimed at preventing or reducing cardiovascular risk.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-01054874
Contributor : Marie Francoise Simon <>
Submitted on : Friday, August 8, 2014 - 5:18:50 PM
Last modification on : Friday, January 10, 2020 - 9:09:54 PM

Identifiers

Collections

Citation

Nizar Serhan, Cendrine Cabou, Céline Verdier, Laeticia Lichtenstein, Nicole Malet, et al.. Chronic pharmacological activation of P2Y13 receptor in mice decreases HDL-cholesterol level by increasing hepatic HDL uptake and bile acid secretion.. BBA - Biochimica et Biophysica Acta, Elsevier, 2013, 1831 (4), pp.719-25. ⟨10.1016/j.bbalip.2012.12.006⟩. ⟨inserm-01054874⟩

Share

Metrics

Record views

151