Role of C-reactive protein in atherogenesis: can the apolipoprotein E knockout mouse provide the answer?
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.
Reifenberg
Kurt
K
Central Laboratory Animal Facility, Johannes Gutenberg University Mainz, Germany.
Lehr
Hans-Anton
HA
Baskal
Daniela
D
Wiese
Elena
E
Schaefer
Stephan C
SC
Black
Steven
S
Samols
David
D
Torzewski
Michael
M
Lackner
Karl J
KJ
Husmann
Matthias
M
Blettner
Maria
M
Bhakdi
Sucharit
S
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
D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D004044:Dietary Proteins; D003165:Complement System Proteins; D002097:C-Reactive Protein