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Human C-Reactive Protein Slows Atherosclerosis Development in a Mouse Model with Human-Like Hypercholesterolemia

Alexander Kovacs, Per Tornvall, Roland Nilsson, Jesper Tegnér, Anders Hamsten and Johan Björkegren
Proceedings of the National Academy of Sciences of the United States of America
Vol. 104, No. 34 (Aug. 21, 2007), pp. 13768-13773
Stable URL: http://www.jstor.org/stable/25436566
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Human C-Reactive Protein Slows Atherosclerosis Development in a Mouse Model with Human-Like Hypercholesterolemia
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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.

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