title: Apolipoprotein A-I protection against atherosclerosis is dependent on genetic background.
abstract: OBJECTIVE
  Inbred mouse strains have different susceptibilities to experimental atherosclerosis. The C57BL/6 strain is among the most sensitive and has, therefore, been the most widely used in atherosclerosis studies, whereas many strains are resistant. The FVB/N strain is highly resistant to atherosclerosis on the apolipoprotein E (apoE)- and low-density lipoprotein (LDL) receptor-deficient backgrounds. High-density lipoprotein and its major apoprotein, apoA-I, have been shown to be protective against atherogenesis on the C57BL/6 background. We here examine the influence of genetic background on the atheroprotective nature of apoA-I.
  
  
  RESULTS
  ApoE-deficient/apoA-I-deficient mice were generated in the C57BL/6 and FVB/N strains from apoE-deficient mice. After 6 to 10 weeks on a Western-type diet, plasma lipids and atherosclerotic lesion size were assessed. Macrophage recruitment, cholesterol regulation, and blood monocyte levels were examined as potential mechanisms driving lesion size differences. FVB/N knockout mice had higher plasma very-LDL/LDL cholesterol than their C57BL/6 counterparts. ApoA-I deficiency decreased very-LDL/LDL cholesterol in C57BL/6 mice but not in FVB/N mice. FVB/N single and double knockout mice had less lesion than C57BL/6 6 to 10 weeks on diet. ApoA-I deficiency augmented lesion development only in C57BL/6 mice. Macrophage recruitment to thioglycollate-treated peritoneum and diet-induced blood monocyte levels reflected the pattern of lesion development among the 4 genotypes. ApoA-I deficiency increased macrophage cholesterol content only in C57BL/6. FVB/N plasma was a better acceptor for macrophage cholesterol efflux than C57BL/6.
  
  
  CONCLUSIONS
  ApoA-I is atheroprotective only in certain genetic contexts. In the C57BL/6 context, but not FVB/N, apoA-I decreases inflammatory macrophage recruitment and monocytosis, contributors to lesion formation.
authors: From the Department of Pathology, University of Chicago, IL.
authors: Timothy J
authors: TJ
authors: Sontag
authors: Paulette A
authors: PA
authors: Krishack
authors: John R
authors: JR
authors: Lukens
authors: Clarissa V
authors: CV
authors: Bhanvadia
authors: Godfrey S
authors: GS
authors: Getz
authors: Catherine A
authors: CA
authors: Reardon
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016632:Apolipoprotein A-I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016122:Brachiocephalic Trunk / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D013045:Species Specificity; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D014280:Triglycerides; D002784:Cholesterol
keywords: cholesterol; cholesterol, HDL; macrophages; mice, inbred strains; monocytes