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

• Published in: Atherosclerosis Vol. 196; no. 1; pp. 248 - 255
• Main Authors: Tennent, Glenys A, Hutchinson, Winston L, Kahan, Melvyn C, Hirschfield, Gideon M, Gallimore, J. Ruth, Lewin, Jackie, Sabin, Caroline A, Dhillon, Amar P, Pepys, Mark B
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.01.2008; Elsevier
• Subjects: Aging; Animals; Apolipoproteins; Apolipoproteins E - genetics; Arteriosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - physiopathology; Biological and medical sciences; Blood and lymphatic vessels; C-reactive protein; C-Reactive Protein - genetics; C-Reactive Protein - physiology; Cardiology. Vascular system; Cardiovascular; Humans; Male; Medical sciences; Mice; Mice, Knockout; Mice, Transgenic; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Thrombosis; Thrombosis - physiopathology; Transgenic mice; C-reactive protein; Apolipoproteins; Thrombosis; Arteriosclerosis; Transgenic mice; Human; Rodentia; Cardiovascular disease; Apolipoprotein; Vascular disease; Vertebrata; Mammalia; Mouse; Animal; Atherosclerosis; C reactive protein
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2007.05.010

Abstract 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.