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Human C-reactive pr...
Human C-reactive protein slows atherosclerosis development in a mouse model with human-like hypercholesterolemia
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- Kovacs, Alexander (author)
- Atherosclerosis Research group KI
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- Tornvall, Per (author)
- Karolinska Institutet
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- Nilsson, Roland, 1977- (author)
- Karolinska Institutet,Linköpings universitet,Tekniska högskolan,Biologiska Beräkningar
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- Tegnér, Jesper, 1962- (author)
- Karolinska Institutet,Linköpings universitet,Tekniska högskolan,Biologiska Beräkningar
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- Hamsten, Anders (author)
- Karolinska Institutet
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- Björkegren, Johan (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2007-08-21
- 2007
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:34, s. 13768-13773
- Related links:
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http://www.pnas.org/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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. © 2007 by The National Academy of Sciences of the USA.
Keyword
- NATURAL SCIENCES
- NATURVETENSKAP
Publication and Content Type
- ref (subject category)
- art (subject category)
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