title: Deficiency of endogenous acute phase serum amyloid A does not affect atherosclerotic lesions in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  Although elevated plasma concentrations of serum amyloid A (SAA) are associated strongly with increased risk for atherosclerotic cardiovascular disease in humans, the role of SAA in the pathogenesis of lesion formation remains obscure. Our goal was to determine the impact of SAA deficiency on atherosclerosis in hypercholesterolemic mice.
  
  
  RESULTS
  Apolipoprotein E-deficient (apoE(-/-)) mice, either wild type or deficient in both major acute phase SAA isoforms, SAA1.1 and SAA2.1, were fed a normal rodent diet for 50 weeks. Female mice, but not male apoE-/- mice deficient in SAA1.1 and SAA2.1, had a modest increase (22%; P≤0.05) in plasma cholesterol concentrations and a 53% increase in adipose mass compared with apoE-/- mice expressing SAA1.1 and SAA2.1 that did not affect the plasma cytokine levels or the expression of adipose tissue inflammatory markers. SAA deficiency did not affect lipoprotein cholesterol distributions or plasma triglyceride concentrations in either male or female mice. Atherosclerotic lesion areas measured on the intimal surfaces of the arch, thoracic, and abdominal regions were not significantly different between apoE-/- mice deficient in SAA1.1 and SAA2.1 and apoE-/- mice expressing SAA1.1 and SAA2.1 in either sex. To accelerate lesion formation, mice were fed a Western diet for 12 weeks. SAA deficiency had effect neither on diet-induced alterations in plasma cholesterol, triglyceride, or cytokine concentrations nor on aortic atherosclerotic lesion areas in either male or female mice. In addition, SAA deficiency in male mice had no effect on lesion areas or macrophage accumulation in the aortic roots.
  
  
  CONCLUSIONS
  The absence of endogenous SAA1.1 and 2.1 does not affect atherosclerotic lipid deposition in apolipoprotein E-deficient mice fed either normal or Western diets.
authors.affiliation: From the Graduate Center for Nutritional Science (M.C.D.B., J.M.W., V.P.N., A.J., P.S., J.C.T., D.R.v.d.W., L.R.T., N.R.W., F.C.D.B.), Saha Cardiovascular Research Center (M.C.D.B., J.M.W., V.P.N., D.L.R., D.A.H., A.B., A.J., P.S., J.C.T., D.R.v.d.W., L.R.T., A.D., N.R.W., F.C.D.B.), and the Departments of Physiology (M.C.D.B.) and Internal Medicine (J.M.W., V.P.N., D.L.R., D.A.H., A.B., A.J., P.S., J.C.T., D.R.v.d.W., L.R.T., A.D., N.R.W., F.C.D.B.), University of Kentucky Medical Center, Lexington, KY; and Department of Veterans Affairs Medical Center, Lexington, KY (D.R.v.d.W., L.R.T.).
authors.forename: Maria C
authors.initials: MC
authors.lastname: De Beer
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Wroblewski
authors.forename: Victoria P
authors.initials: VP
authors.lastname: Noffsinger
authors.forename: Debra L
authors.initials: DL
authors.lastname: Rateri
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Howatt
authors.forename: Anju
authors.initials: A
authors.lastname: Balakrishnan
authors.forename: Ailing
authors.initials: A
authors.lastname: Ji
authors.forename: Preetha
authors.initials: P
authors.lastname: Shridas
authors.forename: Joel C
authors.initials: JC
authors.lastname: Thompson
authors.forename: Deneys R
authors.initials: DR
authors.lastname: van der Westhuyzen
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Tannock
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Webb
authors.forename: Frederick C
authors.initials: FC
authors.lastname: De Beer
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology; D050154:Adiposity; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006937:Hypercholesterolemia / Q000150:complications / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000685:Serum Amyloid A Protein / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D018836:Inflammation Mediators; C489995:Saa2 protein, mouse; D000685:Serum Amyloid A Protein; D014280:Triglycerides; D002784:Cholesterol
keywords: acute phase proteins; atherosclerosis; inflammation; serum amyloid A-deficient mice