| First Author | Kovacs A | Year | 2007 |
| Journal | Proc Natl Acad Sci U S A | Volume | 104 |
| Issue | 34 | Pages | 13768-73 |
| PubMed ID | 17702862 | Mgi Jnum | J:124095 |
| Mgi Id | MGI:3720518 | Doi | 10.1073/pnas.0706027104 |
| Citation | Kovacs A, et al. (2007) Human C-reactive protein slows atherosclerosis development in a mouse model with human-like hypercholesterolemia. Proc Natl Acad Sci U S A 104(34):13768-73 |
| abstractText | Increased baseline values of the acute-phase reactant C-reactive protein (CRP) are significantly associated with future cardiovascular disease, and some in vitro studies have claimed that human CRP (hCRP) has proatherogenic effects. in vivo studies in apolipoprotein E-deficient mouse models, however, have given conflicting results. We bred atherosclerosis-prone mice (Apob(100/100)Ldlr(-/-)), which have human-like hypercholesterolemia, with hCRP transgenic mice (hCRP(+/0)) and studied lesion development at 15, 30, 40, and 50 weeks of age. Atherosclerotic lesions were smaller in hCRP(+/0)Apob(100/100)Ldlr(-/-) mice than in hCRP(0/0)Apob(100/100)Ldlr(-/-) controls, as judged from the lesion surface areas of pinned-out aortas from mice at 40 and 50 weeks of age. In lesions from 40-week-old mice, mRNA expression levels of several genes in the proteasome degradation pathway were higher in hCRP(+/0)Apob(100/100)Ldlr(-/-) mice than in littermate controls, as shown by global gene expression profiles. These results were confirmed by real-time PCR, which also indicated that the activities of those genes were the same at 30 and 40 weeks in hCRP(+/0)Apob(100/100)Ldlr(-/-) mice but were significantly lower at 40 weeks than at 30 weeks in controls. Our results show that hCRP is not proatherogenic but instead slows atherogenesis, possibly through proteasome-mediated protein degradation. |
