title: No reduction of atherosclerosis in C-reactive protein (CRP)-deficient mice.
abstract: C-reactive protein (CRP), a phylogenetically highly conserved plasma protein, is the classical acute phase reactant in humans. Upon infection, inflammation, or tissue damage, its plasma level can rise within hours >1000-fold, providing an early, nonspecific disease indicator of prime clinical importance. In recent years, another aspect of CRP expression has attracted much scientific and public attention. Apart from transient, acute phase-associated spikes in plasma concentration, highly sensitive measurements have revealed stable interindividual differences of baseline CRP values in healthy persons. Strikingly, even modest elevations in stable baseline CRP plasma levels have been found to correlate with a significantly increased risk of future cardiovascular disease. These observations have triggered intense controversies about potential atherosclerosis-promoting properties of CRP. To directly assess potential effects of CRP on atherogenesis, we have generated CRP-deficient mice via gene targeting and introduced the inactivated allele into atherosclerosis-susceptible ApoE(-/-) and LDLR(-/-) mice, two well established mouse models of atherogenesis. Morphometric analyses of atherosclerotic plaques in CRP-deficient animals revealed equivalent or increased atherosclerotic lesions compared with controls, an experimental result, which does not support a proatherogenic role of CRP. In fact, our data suggest that mouse CRP may even mediate atheroprotective effects, adding a cautionary note to the idea of targeting CRP as therapeutic intervention against progressive cardiovascular disease.
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig Research Center for Civilization Diseases, University Leipzig, Liebigstrasse 27, D-04103 Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Teupser
authors.forename: Odile
authors.initials: O
authors.lastname: Weber
authors.forename: Tata Nageswara
authors.initials: TN
authors.lastname: Rao
authors.forename: Kristina
authors.initials: K
authors.lastname: Sass
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.forename: Hans Jörg
authors.initials: HJ
authors.lastname: Fehling
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D011973:Receptors, LDL; D002097:C-Reactive Protein