title: ApoE-dependent modulation of HDL and atherosclerosis by G2A in LDL receptor-deficient mice independent of bone marrow-derived cells.
abstract: OBJECTIVE
  Deletion of the lysophospholipid-sensitive receptor, G2A, in low-density lipoprotein receptor knockout (LDLR(-/-)) mice elevates plasma high-density lipoprotein (HDL) cholesterol and suppresses atherosclerosis. However, chemotactic action of G2A in monocytes/macrophages, in addition to its modulatory effect on HDL, may contribute to the proatherogenic action of G2A.
  
  
  RESULTS
  We determined that deletion of G2A in LDLR(-/-) mice increases the ApoA1, ApoE, and cholesterol content of plasma HDL fractions. Hepatocytes were shown to express G2A and hepatocytes from G2A-deficient LDLR(-/-) mice secreted more ApoA1 and ApoE in HDL fractions compared to their G2A-sufficient counterparts. The atheroprotective and HDL modulatory effects of G2A deficiency were dependent on the presence of ApoE, as deletion of G2A in ApoE(-/-) and ApoE(-/-)LDLR(-/-) mice failed to raise HDL and did not suppress atherosclerosis. G2A deficiency in bone marrow-derived cells of LDLR(-/-) mice had no effect on atherosclerosis or HDL, whereas G2A deficiency in resident tissues was sufficient to raise HDL and suppress atherosclerosis.
  
  
  CONCLUSIONS
  These data demonstrate that the chemotactic function of G2A in bone marrow-derived monocytes does not modulate atherosclerosis in LDLR(-/-) mice and suggest an ApoE-dependent function for G2A in the control of hepatic HDL metabolism that might contribute to its proatherogenic action.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham AL 35294-2170, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Parks
authors.forename: Roshni
authors.initials: R
authors.lastname: Srivastava
authors.forename: Shaohua
authors.initials: S
authors.lastname: Yu
authors.forename: Janusz H S
authors.initials: JH
authors.lastname: Kabarowski
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism*; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002633:Chemotaxis; D008076:Cholesterol, HDL / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D018797:Cell Cycle Proteins; D008076:Cholesterol, HDL; C115270:G2A receptor; D008075:Lipoproteins, HDL; D043562:Receptors, G-Protein-Coupled; D011973:Receptors, LDL