title: Human C-reactive protein does not promote atherosclerosis in transgenic rabbits.
abstract: BACKGROUND
  Although there is a statistically significant association between modestly raised baseline plasma C-reactive protein (CRP) values and future cardiovascular events, the debate is still unsettled in regard to whether CRP plays a causal role in the pathogenesis of atherosclerosis.
  
  
  RESULTS
  We generated 2 lines of transgenic (Tg) rabbits expressing human CRP (hCRP). The plasma levels of hCRP in hCRP-Tg-1 and hCRP-Tg-2 rabbits were 0.4+/-0.13 (n=14) and 57.8+/-20.6 mg/L (n=12), respectively. In addition, hCRP isolated from Tg rabbit plasma exhibited the ability to activate the rabbit complement. To define the role of hCRP in atherosclerosis, we compared the susceptibility of hCRP-Tg rabbits to cholesterol-rich diet-induced aortic and coronary atherosclerosis with that of non-Tg rabbits. After being fed with a cholesterol-rich diet for 16 weeks, Tg and non-Tg rabbits developed similar hypercholesterolemia and lesion sizes in both aortic and coronary arteries. Immunohistochemical staining and Western blotting revealed that hCRP was indeed present in the lesions but did not affect macrophage accumulation and smooth muscle cell proliferation of the lesions.
  
  
  CONCLUSIONS
  Neither high nor low plasma concentrations of hCRP affected aortic or coronary atherosclerosis lesion formation in hCRP-Tg rabbits.
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-City, Yamanashi, 409-3898, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Koike
authors.forename: Shuji
authors.initials: S
authors.lastname: Kitajima
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Nishijima
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ozaki
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Morimoto
authors.forename: Teruo
authors.initials: T
authors.lastname: Watanabe
authors.forename: Sucharit
authors.initials: S
authors.lastname: Bhakdi
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Asada
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.forename: Jianglin
authors.initials: J
authors.lastname: Fan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D050197:Atherosclerosis / Q000175:diagnosis / Q000209:etiology*; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis / Q000502:physiology*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D006801:Humans; D008297:Male; D011817:Rabbits
chemical_list: D015415:Biomarkers; D002791:Cholesterol, Dietary; D002097:C-Reactive Protein