title: Role of C-reactive protein in atherogenesis: can the apolipoprotein E knockout mouse provide the answer?
abstract: OBJECTIVE
  Human C-reactive protein (CRP) was reported to accelerate atherosclerotic lesion development in male but not in female apolipoprotein E (apoE) knockout mice. Here, mice expressing rabbit CRP (rbCRP) were crossbred onto apoE knockout animals, and the effect on atherogenesis was studied.
  
  
  RESULTS
  Hemolytic complement activity could not be detected in apoE knockout mice. Furthermore, in contrast to human complement, neither rabbit nor human CRP complexed to modified low-density lipoprotein-activated murine complement. At 52 weeks, rbCRP levels were similar in male and female transgenic animals. Serum cholesterol levels were equivalent in female animals irrespective of rbCRP expression, whereas rbCRP-positive males had significantly higher serum cholesterol levels than the rbCRP-negative counterparts. All mice exhibited extensive atherosclerotic lesions, as studied en face, and no differences were noted between rbCRP-negative and rbCRP-positive animals. Atherosclerotic luminal obstruction of aortic arch and first-order neck branches did not differ significantly between rbCRP-positive and rbCRP-negative mice. There was no correlation between rbCRP levels and atherosclerotic lesion formation.
  
  
  CONCLUSIONS
  No marked effect of rbCRP on the formation of moderately advanced atherosclerotic lesions could be discerned in the apoE knockout mouse. Because of the oddities of the mouse complement system, however, this may not be a good model to investigate the role of CRP in human atherosclerosis.
authors.affiliation: Central Laboratory Animal Facility, Johannes Gutenberg University Mainz, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Reifenberg
authors.forename: Hans-Anton
authors.initials: HA
authors.lastname: Lehr
authors.forename: Daniela
authors.initials: D
authors.lastname: Baskal
authors.forename: Elena
authors.initials: E
authors.lastname: Wiese
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Schaefer
authors.forename: Steven
authors.initials: S
authors.lastname: Black
authors.forename: David
authors.initials: D
authors.lastname: Samols
authors.forename: Michael
authors.initials: M
authors.lastname: Torzewski
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
authors.forename: Matthias
authors.initials: M
authors.lastname: Husmann
authors.forename: Maria
authors.initials: M
authors.lastname: Blettner
authors.forename: Sucharit
authors.initials: S
authors.lastname: Bhakdi
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics* / Q000276:immunology; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002097:C-Reactive Protein / Q000235:genetics / Q000276:immunology*; D008078:Cholesterol, LDL / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology; D004044:Dietary Proteins / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011817:Rabbits; D013045:Species Specificity; D019076:Transgenes / Q000502:physiology
chemical_list: D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D004044:Dietary Proteins; D003165:Complement System Proteins; D002097:C-Reactive Protein