Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, UK. g.tennent@medsch.ucl.ac.uk
The pathogenic significance, if any, of the epidemiological association between baseline C-reactive protein (CRP) values and future atherothrombotic events is not known. We therefore investigated spontaneous atherosclerosis and atherothrombosis, and systemic markers of inflammation (acute phase proteins), in aged, normal diet-fed, male apolipoprotein E deficient (apoE(-/-)) mice with and without transgenic expression of human CRP. At 18 months of age, aortic atherosclerosis was extensive but with no significant difference in plaque size between C57BL/6apoE(-/-) mice with (apoE(-/-)-hCRP(+)) and without transgenic human CRP (apoE(-/-)). Atherosclerotic lesions in brachiocephalic arteries were typically complex and layered, with extensive fibrotic-cholesterol deposits, calcification and occasional recent intraplaque haemorrhage and thrombus, but with no significant overall differences between apoE(-/-) and apoE(-/-)-hCRP(+) animals. Concentrations of mouse serum amyloid P component (SAP) were essentially normal throughout and did not differ between apoE(-/-) and apoE(-/-)-hCRP(+) mice, or between wild-type (apoE(+/+)) and apoE(-/-) mice, regardless of human CRP expression. Mouse serum amyloid A protein (SAA), and human CRP concentrations were modestly but significantly higher in apoE(-/-)-hCRP(+) than in apoE(+/+)-hCRP(+) animals, but mouse SAA values were unaffected by transgenic expression of human CRP in either background. Thus, there was no evidence in this 18 month study of apoE(-/-), and control apoE(+/+) mice, that transgenic human CRP was pro-atherogenic, pro-inflammatory or pro-atherothrombotic.