title: Reduced atherosclerotic lesions in P2Y1/apolipoprotein E double-knockout mice: the contribution of non-hematopoietic-derived P2Y1 receptors.
abstract: BACKGROUND
  The P2Y(1) receptor plays a key role in arterial thrombosis and is widely expressed in many cell types involved in atherosclerosis. The aim of this study was to evaluate its potential involvement in the development of atherosclerotic lesions.
  
  
  RESULTS
  Apolipoprotein E-deficient (ApoE(-/-)) and P2Y(1)(-/-)/ApoE(-/-) mice were maintained on regular chow for 17 or 30 weeks before analysis of atherosclerotic lesions. At 17 weeks, lesions in the aortic sinus and entire aorta were smaller in P2Y(1)(-/-)/ApoE(-/-) compared with those in ApoE(-/-) animals. At 30 weeks, the aortic sinus lesions in P2Y(1)(-/-)/ApoE(-/-) mice were still diminished in size and displayed reduced inflammation, reflected by decreased macrophage infiltration and diminished VCAM-1 immunostaining, compared with those in ApoE(-/-) mice. They also had a lower smooth muscle cell content. Unexpectedly, bone marrow transplantation showed that the absence of the P2Y(1) receptor in blood cells only led to no significant modification of the lesion compared with control ApoE(-/-) reconstituted animals. Conversely, the absence of the P2Y(1) receptor except in blood cells resulted in a reduction in lesion size similar to that in control P2Y(1)(-/-)/ApoE(-/-) reconstituted mice, pointing to a role of non-hematopoietic-derived P2Y(1) receptors, most likely the endothelial or smooth muscle cell P2Y(1) receptors. In addition, although this was not statistically significant, plasma cholesterol levels were consistently decreased in P2Y(1)(-/-) animals, suggesting that a modification of lipid metabolism could be responsible for the observed phenotype.
  
  
  CONCLUSIONS
  The P2Y(1) receptor contributes to atherosclerosis, primarily through its role in non-hematopoietic-derived cells.
authors.affiliation: INSERM U.311, EFS-Alsace, and Université Louis Pasteur, Strasbourg, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Hechler
authors.forename: Monique
authors.initials: M
authors.lastname: Freund
authors.forename: Catherine
authors.initials: C
authors.lastname: Ravanat
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Magnenat
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cazenave
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology*; D001773:Blood Cells / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism / Q000502:physiology; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1; D012850:Sinus of Valsalva / Q000378:metabolism / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D008055:Lipids; C546383:P2ry1 protein, mouse; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1