Human C-reactive protein slows atherosclerosis development in a mouse model with human-like hypercholesterolemia

Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13768-73. doi: 10.1073/pnas.0706027104. Epub 2007 Aug 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins B / deficiency
  • Apolipoproteins B / genetics
  • Apolipoproteins B / metabolism
  • Atherosclerosis / complications
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology*
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism*
  • Disease Models, Animal
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / genetics
  • Hypercholesterolemia / metabolism*
  • Hypercholesterolemia / pathology*
  • Mice
  • Mice, Knockout
  • RNA, Messenger / genetics


  • Apolipoproteins B
  • RNA, Messenger
  • C-Reactive Protein