C-Reactive Protein Accelerates the Progression of Atherosclerosis in Apolipoprotein E–Deficient Mice

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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. Methods and 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 o...