No Reduction of Atherosclerosis in C-reactive Protein (CRP)-deficient Mice

• Published in: The Journal of biological chemistry Vol. 286; no. 8; pp. 6272 - 6279
• Main Authors: Teupser, Daniel, Weber, Odile, Rao, Tata Nageswara, Sass, Kristina, Thiery, Joachim, Fehling, Hans Jörg
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.02.2011; American Society for Biochemistry and Molecular Biology
• Subjects: Acute Phase Proteins; Animals; Apolipoproteins; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; Atherosclerosis; Atherosclerosis - genetics; Atherosclerosis - metabolism; C-reactive Protein; C-Reactive Protein - genetics; C-Reactive Protein - metabolism; Disease Models, Animal; Gene Knock-out; Humans; Inflammation; Mice; Mice, Knockout; Molecular Bases of Disease; Mouse Genetics; Receptors, LDL - genetics; Receptors, LDL - metabolism; Acute Phase Proteins; Atherosclerosis; Gene Knock-out; Mouse Genetics; C-reactive Protein; Inflammation; Apolipoproteins
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.161414

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.