title: Transgenic human CRP is not pro-atherogenic, pro-atherothrombotic or pro-inflammatory in apoE-/- mice.
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.
authors.affiliation: Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, UK. Electronic address: g.tennent@medsch.ucl.ac.uk.
authors.forename: Glenys A
authors.initials: GA
authors.lastname: Tennent
authors.affiliation: Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, UK.
authors.forename: Winston L
authors.initials: WL
authors.lastname: Hutchinson
authors.affiliation: Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, UK.
authors.forename: Melvyn C
authors.initials: MC
authors.lastname: Kahan
authors.affiliation: Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, UK.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Hirschfield
authors.affiliation: Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, UK.
authors.forename: J Ruth
authors.initials: JR
authors.lastname: Gallimore
authors.affiliation: Electron Microscopy Unit, University College London, UK.
authors.forename: Jackie
authors.initials: J
authors.lastname: Lewin
authors.affiliation: Department of Primary Care and Population Sciences, University College London, UK.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.affiliation: Department of Histopathology, University College London, UK.
authors.forename: Amar P
authors.initials: AP
authors.lastname: Dhillon
authors.affiliation: Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, UK.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Pepys
mesh_terms: D000375:Aging; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013927:Thrombosis / Q000503:physiopathology*
chemical_list: D001057:Apolipoproteins E; D002097:C-Reactive Protein