Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13768-73. Epub 2007 Aug 16.

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

Author information

1
Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden.

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(100/100)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.

PMID:
17702862
PMCID:
PMC1959457
DOI:
10.1073/pnas.0706027104
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center