title: Loss of the lysophosphatidylcholine effector, G2A, ameliorates aortic atherosclerosis in low-density lipoprotein receptor knockout mice.
abstract: OBJECTIVE
  Lysophosphatidylcholine is a major product of low-density lipoprotein (LDL) oxidation and secretory phospholipase A2-mediated lipid hydrolysis within atherosclerotic lesions. The G2A receptor mediates chemotaxis of cultured macrophages and T cells to lysophosphatidylcholine, supporting a pro-atherogenic role for this receptor in vivo. We investigated the ability of G2A to modulate atherosclerosis in mice.
  
  
  RESULTS
  We measured atherosclerosis in G2A+/+ and G2A-/- LDL receptor knockout (LDLR-/-) mice. Consistent with a previous study, early lesion size at the aortic sinus was unaffected by G2A deficiency. However, G2A deficiency attenuated lesion progression at this site (42% to 44% reduction in average lesion area) and led to robust suppression of atherosclerosis throughout the aorta after short and extended periods of diet intervention (reduction in aortic lesion coverage: 62% to 73% at 9 weeks, 75% to 84% at 20 weeks). In G2A-/- LDLR-/- mice, intimal macrophage accumulation at lesion-prone sites of the aorta was significantly reduced in the absence of any detectable effect on T cell recruitment. Examination of lipoprotein profiles revealed elevated levels of circulating high-density lipoprotein (HDL) cholesterol in G2A-/- LDLR-/- mice compared with their G2A+/+ LDLR-/- counterparts after extended periods of diet intervention (54% increase in mean HDL cholesterol concentration).
  
  
  CONCLUSIONS
  G2A provides a pro-atherogenic stimulus in vivo consistent with its chemotactic action but to which a pleiotropy of effects, including modulation of lipoprotein metabolism, may also contribute.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, 19th St S, Birmingham, AL 35294-2170, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Parks
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Janusz H S
authors.initials: JH
authors.lastname: Kabarowski
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006937:Hypercholesterolemia / Q000503:physiopathology; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D012850:Sinus of Valsalva / Q000378:metabolism / Q000473:pathology; D017539:Tunica Intima / Q000473:pathology
chemical_list: D018797:Cell Cycle Proteins; D008076:Cholesterol, HDL; C115270:G2A receptor; D008244:Lysophosphatidylcholines; D043562:Receptors, G-Protein-Coupled; D011973:Receptors, LDL