title: Serum Amyloid A Facilitates Early Lesion Development in Ldlr-/- Mice.
abstract: BACKGROUND
  Atherosclerosis is a chronic inflammatory disorder, and several studies have demonstrated a positive association between plasma serum amyloid A (SAA) levels and cardiovascular disease risk. The aim of the study was to examine whether SAA has a role in atherogenesis, the underlying basis of most cardiovascular disease.
  
  
  RESULTS
  Mice globally deficient in acute-phase isoforms Saa1 and Saa2 (Saa(-/-)) were crossed to Ldlr(-/-) mice (Saa(-/-)Ldlr(-/-)). Saa(-/-)Ldlr(-/-) mice demonstrated a 31% reduction in lesional area in the ascending aorta but not in the aortic root or innominate artery after consuming a high-fat, high-cholesterol Western-type diet for 6 weeks. The lesions were predominantly macrophage foam cells. The phenotype was lost in more mature lesions in mice fed a Western-type diet for 12 weeks, suggesting that SAA is involved in early lesion development. The decreased atherosclerosis in the Saa(-/-)Ldlr(-/-) mice occurred despite increased levels of blood monocytes and was independent of plasma lipid levels. SAA is produced predominantly by hepatocytes and macrophages. To determine which source of SAA may have a dominant role in lesion development, bone marrow transplantation was performed. Ldlr(-/-) mice that received bone marrow from Saa(-/-)Ldlr(-/-) mice had slightly reduced ascending aorta atherosclerosis compared with Saa(-/-)Ldlr(-/-) mice receiving bone marrow from Ldlr(-/-) mice, indicating that the expression of SAA by macrophages may have an important influence on atherogenesis.
  
  
  CONCLUSIONS
  The results indicate that SAA produced by macrophages promotes early lesion formation in the ascending aorta.
authors.affiliation: Molecular Pathogenesis and Molecular Medicine Graduate Program, University of Chicago, IL (P.A.K., C.A.R.).
authors.forename: Paulette A
authors.initials: PA
authors.lastname: Krishack
authors.affiliation: Department of Pathology, University of Chicago, IL (C.V.B., J.L., T.J.S., G.S.G., C.A.R.).
authors.forename: Clarissa V
authors.initials: CV
authors.lastname: Bhanvadia
authors.affiliation: Department of Pathology, University of Chicago, IL (C.V.B., J.L., T.J.S., G.S.G., C.A.R.).
authors.forename: John
authors.initials: J
authors.lastname: Lukens
authors.affiliation: Department of Pathology, University of Chicago, IL (C.V.B., J.L., T.J.S., G.S.G., C.A.R.).
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Sontag
authors.affiliation: Graduate Center for Nutritional Science, Saha Cardiovascular Research Center, Lexington, KY (M.C.D.B.) Department of Physiology, University of Kentucky Medical Center, Lexington, KY (M.C.D.B.).
authors.forename: Maria C
authors.initials: MC
authors.lastname: De Beer
authors.affiliation: Department of Pathology, University of Chicago, IL (C.V.B., J.L., T.J.S., G.S.G., C.A.R.).
authors.forename: Godfrey S
authors.initials: GS
authors.lastname: Getz
authors.affiliation: Molecular Pathogenesis and Molecular Medicine Graduate Program, University of Chicago, IL (P.A.K., C.A.R.) Department of Pathology, University of Chicago, IL (C.V.B., J.L., T.J.S., G.S.G., C.A.R.).
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Reardon
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood* / Q000235:genetics / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics / Q000473:pathology; D016026:Bone Marrow Transplantation; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005487:Foam Cells / Q000378:metabolism* / Q000473:pathology; D005838:Genotype; D008055:Lipids / Q000097:blood; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D000685:Serum Amyloid A Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D008055:Lipids; D011973:Receptors, LDL; C489995:Saa2 protein, mouse; D000685:Serum Amyloid A Protein
keywords: atherosclerosis; macrophages; monocytes; serum amyloid A