title: C-reactive protein accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice.
abstract: BACKGROUND
  Plasma C-reactive protein (CRP) concentration is a strong predictor of atherosclerosis. However, to date, there is no in vivo evidence that CRP is proatherogenic.
  
  
  RESULTS
  We studied the effect of human CRP transgene (tg) expression, under basal and turpentine-stimulated conditions, on atherosclerosis in apolipoprotein (apo) E-/- mice. Aortic atherosclerotic lesions in 29-week-old male mice were 48% larger (P<0.02) in turpentine-treated mice and 34% larger (P<0.05) in untreated CRPtg+/0/apoE-/- mice. Turpentine treatment per se did not affect the extent of atherosclerosis in CRP transgenic or nontransgenic apoE-/- mice. Transgenic mice exhibited lower plasma complement C3 but increased deposition of CRP and C3 in the lesions, which suggests that CRP stimulated activation of complement within the lesion. There was more intense and widespread vascular cell adhesion molecule-1 and collagen staining in the lesions of CRPtg+/0/apoE-/- mice than in CRPtg0/0/apoE-/- littermates. Lesions of CRPtg+/0/apoE-/- mice contained increased angiotensin type 1 receptor (AT1-R) transcripts and displayed increased AT1-R immunostaining compared with those of CRPtg0/0/apoE-/- mice. There was no difference in blood pressure in the 2 types of mice, which indicates that the proatherogenic effect of CRP-associated AT1-R overexpression is local and not mediated by its hypertensive properties.
  
  
  CONCLUSIONS
  Human CRP transgene expression causes accelerated aortic atherosclerosis in apoE-/- mice. CRP was detected in the lesion, which was associated with increased C3 deposition and increased AT1-R, vascular cell adhesion molecule-1, and collagen expression. These data document a proatherogenic role for CRP in vivo.
authors.affiliation: Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Tex 77030, USA.
authors.forename: Antoni
authors.initials: A
authors.lastname: Paul
authors.forename: Kerry W S
authors.initials: KW
authors.lastname: Ko
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.forename: Vijay
authors.initials: V
authors.lastname: Yechoor
authors.forename: Mark A
authors.initials: MA
authors.lastname: McCrory
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Szalai
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chan
mesh_terms: D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology*; D002097:C-Reactive Protein / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D003176:Complement C3 / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010641:Phenotype; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E; D003176:Complement C3; D044140:Receptor, Angiotensin, Type 1; D002097:C-Reactive Protein; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse