Increased atherosclerosis in P2Y13/apolipoprotein E double-knockout mice: contribution of P2Y13 to reverse cholesterol transport

Cardiovascular Research
Laeticia LichtensteinLaurent O Martinez

Abstract

High-density lipoproteins (HDLs) protect against atherosclerosis mainly due to their function in hepatobiliary reverse cholesterol transport (RCT). This is a process whereby excess cholesterol from peripheral tissues is transported by HDL particles to the liver for further metabolism and biliary excretion. Hepatic uptake of HDL holoparticles involves the P2Y13 receptor, independently of the selective cholesteryl ester uptake mediated by scavenger receptor class B, type I (SR-BI). Accordingly, P2Y13-deficient mice (P2Y13 (-/-)) have impaired RCT. This study assessed whether P2Y13 deficiency would affect atherosclerotic development. P2Y13 (-/-) mice were crossbred with atherosclerosis-prone apoE(-/-) mice. When 15 weeks old, P2Y13 (-/-)/apoE(-/-) mice had more aortic sinus lesions than apoE(-/-) mice. Bone marrow transplantation showed that the absence of the P2Y13 receptor in blood cells did not lead to significantly greater atherosclerotic plaque size formation compared with control apoE(-/-) reconstituted animals. Conversely, the absence of the P2Y13 receptor, except in blood cells, resulted in lesion sizes similar to that in P2Y13 (-/-)/apoE(-/-) reconstituted mice, pointing to a role for non-haematopoietic-derived P2Y13. Une...Continue Reading

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Citations

Jul 5, 2015·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·J M LaparraA Cilla
Nov 1, 2015·Neuropharmacology·Ivar von Kügelgen, Kristina Hoffmann
Jun 27, 2017·Pharmacology & Therapeutics·Akiyuki NishimuraMotohiro Nishida
May 16, 2017·Current Opinion in Lipidology·Laurent O MartinezBertrand Perret
Nov 30, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Silvia González-RamosLisardo Boscá
Apr 1, 2020·International Journal of Molecular Sciences·Erandi Velázquez-MirandaFrancisco G Vázquez-Cuevas
Apr 1, 2016·Current Opinion in Lipidology·Arnold von Eckardstein, Lucia Rohrer

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