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Adding to the controversy: Continuously‐infused human C‐reactive protein reduces atherosclerosis in apolipoprotein E‐deficient mice
Author(s) -
Ortiz Miguel A,
Sosa Marcelo J,
Walker Candace L,
Woods John R,
Campana Gonzalo L,
Labarrere Carlos A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.174.8
Subject(s) - apolipoprotein b , placebo , medicine , c reactive protein , aorta , aortic root , aortic arch , genetically modified mouse , apolipoprotein e , abdominal aorta , endocrinology , cardiology , inflammation , gastroenterology , transgene , pathology , chemistry , cholesterol , biochemistry , gene , disease , alternative medicine
The role of C‐reactive protein (CRP) in atherosclerosis mouse models remains controversial, with studies showing both proatherogenic and no effects. We hypothesized that the discrepancies might relate to the use of azide‐ or endotoxin‐contaminated native ( n ) CRP, its episodic administration, to the use of CRP transgenic vs. non‐transgenic mice, or to biased sampling of the aorta in evaluating atherosclerotic lesions. We administered azide‐ and endotoxin‐free human n CRP (n=11) or placebo (n=11) to 12‐week‐old apolipoprotein E‐deficient (apoE −/− ) male mice as a continuous infusion for 4 weeks (20.4 μg/day). Animals treated with n CRP developed fewer lesions (7.24 ± 1.59%) in the whole aorta than controls (9.90 ± 2.11%) (p= 0.0026; R 2 = 0.3578). When aortic regions were analyzed separately, the extent of atherosclerotic lesions showed significant differences for n CRP‐treated vs. controls in the thoraco‐abdominal region (3.14 ± 1.27% vs. 4.67 ± 1.89%) (p = 0.0322; R 2 =0.2004); but the differences were not significant in the aortic arch (3.71 ±1.15% vs. 4.63 ± 1.16%) (p = 0.0715; R 2 = 0.1465), the iliac region (0.40 % ± 0.35 vs. 0.62; ± 0.30%) (p = 0.1247; R 2 = 0.1086), or the aortic root (65.02 ± 7.81% vs. 64.71± 9.65%) (p= 0.9393; R 2 = 0.0004). These comparisons show an unexpected reduction of atherosclerosis in n CRP‐treated mice. They also emphasize the methodological importance of examining the whole aorta, rather than arbitrarily selected regions, to gain a valid understanding of atherosclerosis in this model.