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

Alexander Kovacs, Per Tornvall, Roland Nilsson, Jesper Tegner, Anders Hamsten, Johan Björkegren*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

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 100/100Ldlr-/-), 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 Apob100/100Ldlr-/- mice than in hCRP0/0Apob100/100Ldlr-/- 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 +/0Apob100/100Ldlr-/- 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+/0Apob 100/100Ldlr-/- 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.

Original languageEnglish (US)
Pages (from-to)13768-13773
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number34
DOIs
StatePublished - Aug 21 2007

Keywords

  • Acute-phase protein
  • Apolipoprotein B100
  • Coronary artery disease
  • Low-density lipoprotein
  • Plaques

ASJC Scopus subject areas

  • General

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