C-Reactive Protein Accelerates the Progression of Atherosclerosis in Apolipoprotein E–Deficient Mice
- 10 February 2004
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 109 (5), 647-655
- https://doi.org/10.1161/01.cir.0000114526.50618.24
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 (PP+/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.Keywords
This publication has 34 references indexed in Scilit:
- Increased Thrombosis After Arterial Injury in Human C-Reactive Protein–Transgenic MiceCirculation, 2003
- C-Reactive Protein Upregulates Angiotensin Type 1 Receptors in Vascular Smooth MuscleCirculation, 2003
- Markers of Inflammation and Cardiovascular DiseaseCirculation, 2003
- C-Reactive Protein Predicts Progression of Atherosclerosis Measured at Various Sites in the Arterial TreeStroke, 2002
- Inflammation in atherosclerosisNature, 2002
- Generation of C-Reactive Protein and Complement Components in Atherosclerotic PlaquesThe American Journal of Pathology, 2001
- Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E–deficient miceJCI Insight, 2000
- Reduced progression of atherosclerosis in apolipoprotein E-deficient mice with phenylhydrazine-induced anemiaAtherosclerosis, 1999
- Role of angiotensin II in extracellular matrix and transforming growth factor-β1 expression in hypertensive ratsEuropean Journal of Pharmacology: Molecular Pharmacology, 1994
- Spontaneous Hypercholesterolemia and Arterial Lesions in Mice Lacking Apolipoprotein EScience, 1992