Transgenic human CRP is not pro-atherogenic, pro-atherothrombotic or pro-inflammatory in apoE−/− mice

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.