title: The capacity of group V sPLA2 to increase atherogenicity of ApoE-/- and LDLR-/- mouse LDL in vitro predicts its atherogenic role in vivo.
abstract: OBJECTIVE
  In vitro data indicate that human LDL modified by Group V secretory phospholipase A(2) (GV sPLA(2)) is proatherogenic. Consistent with this, gain and loss of function studies demonstrated that GV sPLA(2) promotes atherosclerosis in LDLR(-/-) mice. The current study investigates whether GV sPLA(2) promotes atherosclerotic processes in apoE(-/-) mice.
  
  
  RESULTS
  LDL (d=1.019 to 1.063) from apoE(-/-) and LDLR(-/-) mice fed chow or Western diet were hydrolyzed by GV sPLA(2). Phosphatidylcholine on LDL from LDLR(-/-) mice fed either a chow or Western diet was hydrolyzed to a greater extent (61.1+/-0.4% and 45.3+/-4.6%) than the corresponding fractions from apoE(-/-) mice (41.7+/-3.6% and 39.4+/-1.2%). ApoE(-/-) LDL induced macrophage foam cell formation in vitro without modification by GV sPLA(2), whereas hydrolysis of LDLR(-/-) LDL was a prerequisite for foam cell formation. In contrast to findings in LDLR(-/-) mice, GV sPLA(2) deficiency did not significantly reduce atherosclerosis in apoE(-/-) mice, although collagen content was significantly reduced in lesions of apoE(-/-) mice lacking GV sPLA(2).
  
  
  CONCLUSIONS
  The ability of GV sPLA(2) to promote atherosclerotic lipid deposition in apoE(-/-) and LDLR(-/-) mice may be related to its ability to increase the atherogenic potential of LDL from these mice as assessed in vitro.
authors.affiliation: Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536-0200, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Boyanovsky
authors.forename: Melissa
authors.initials: M
authors.lastname: Zack
authors.forename: Kathy
authors.initials: K
authors.lastname: Forrest
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Webb
mesh_terms: D000818:Animals; D001011:Aorta / Q000201:enzymology* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D005487:Foam Cells / Q000201:enzymology; D054505:Group V Phospholipases A2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006868:Hydrolysis; D008077:Lipoproteins, LDL / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010713:Phosphatidylcholines / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D013109:Sphingomyelins / Q000378:metabolism; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; D004041:Dietary Fats; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D011973:Receptors, LDL; D013109:Sphingomyelins; D003094:Collagen; D054505:Group V Phospholipases A2; C516300:Pla2g5 protein, mouse