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No effect of C-reactive protein on early atherosclerosis development in apolipoprotein E*3-Leiden/human C-reactive protein transgenic mice

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Author: Trion, A. · Maat, M.P.M. de · Jukema, J.W. · Laarse, A. van der · Maas, M.C. · Offerman, E.H. · Havekes, L.M. · Szalai, A.J. · Princen, H.M.G. · Emeis, J.J.
Type:article
Date:2005
Institution: TNO Kwaliteit van Leven
Source:Arteriosclerosis, Thrombosis, and Vascular Biology, 8, 25, 1635-1640
Identifier: 238640
doi: doi:10.1161/01.ATV.0000171992.36710.1e
Keywords: Biology · Biomedical Research · Atherosclerosis · C-reactive protein · Inflammation · Mouse · Transgene · Acute phase protein · Apolipoprotein E3 Leiden · Biological marker · C reactive protein · Cholesterol · Unclassified drug · Animal experiment · Animal model · Animal tissue · Atherogenesis · Blood sampling · Cardiovascular risk · Cholesterol blood level · Cholesterol diet · Controlled study · Enzyme linked immunosorbent assay · Experimental model · Histopathology · Hypercholesterolemia · Immunohistochemistry · Inflammation · Mouse strain · Nonhuman · Pathophysiology · Protein blood level · Protein expression · Protein function · Transgenic mouse · Animals · Apolipoprotein E3 · Apolipoproteins E · Atherosclerosis · Biological Markers · Body Weight · C-Reactive Protein · Cholesterol · Early Diagnosis · Eating · Endothelium, Vascular · Female · Humans · Hypercholesterolemia · Male · Mice · Mice, Transgenic · Monocytes · Risk Factors · Severity of Illness Index

Abstract

Objective - C-reactive protein (CRP) has been associated with risk of cardiovascular disease. It is not clear whether CRP is causally involved in the development of atherosclerosis. Mouse CRP is not expressed at high levels under normal conditions and increases in concentration only several-fold during an acute phase response. Because the dynamic range of human CRP is much larger, apolipoprotein E*3-Leiden (E3L) transgenic mice carrying the human CRP gene offer a unique model to study the role(s) of CRP in atherosclerosis development. Methods and Results - Atherosclerosis development was studied in 15 male and 15 female E3L/CRP mice; E3L transgenic littermates were used as controls. The mice were fed a hypercholesterolemic diet to induce atherosclerosis development. Cholesterol exposure did not differ between E3L/CRP and E3L mice. Plasma CRP levels were on average 10.2±6.5 mg/L in male E3L/CRP mice, 0.2±0.1 mg/L in female E3L/CRP mice, and undetectable in E3L mice. Quantification of atherosclerosis showed that lesion area in E3L/CRP mice was not different from that in E3L mice. Conclusion - This study demonstrates that mildly elevated levels of CRP in plasma do not contribute to the development of early atherosclerosis in hypercholesterolemic E3L/CRP mice. © 2005 American Heart Association, Inc. Chemicals / CAS: C reactive protein, 9007-41-4; cholesterol, 57-88-5; Apolipoprotein E3; Apolipoproteins E; Biological Markers; C-Reactive Protein, 9007-41-4; Cholesterol, 57-88-5