on May 26, 2005
Published online before print May 26, 2005, doi: 10.1161/01.ATV.0000171992.36710.1e
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on November 3, 2004
Accepted on April 3, 2005
No Effect of C-Reactive Protein on Early Atherosclerosis Development in Apolipoprotein E*3-Leiden/Human C-Reactive Protein Transgenic Mice
A. Trion ;
From the Department of Cardiology (A.T., J.W.J., A.v.d.L.), Leiden University Medical Center, Leiden, the Netherlands; Biomedical Research (A.T., M.P.M.d.M., M.C.M., E.H.O., L.M.H., H.M.G.P., J.J.E.), TNO, Leiden, the Netherlands; the Department of Hematology (M.P.M.d.M.), Erasmus Medical Center, Rotterdam, the Netherlands; and the Department of Medicine (A.J.S.), University of Alabama at Birmingham.
* To whom correspondence should be addressed. E-mail: jj.emeis{at}pg.tno.nl.
Objective--C-reactive protein (CRP) has been associated with risk of cardiovascular disease. It is not clear whether CRP is causally involved in the development of atherosclerosis. Mouse CRP is not expressed at high levels under normal conditions and increases in concentration only several-fold during an acute phase response. Because the dynamic range of human CRP is much larger, apolipoprotein E*3-Leiden (E3L) transgenic mice carrying the human CRP gene offer a unique model to study the role(s) of CRP in atherosclerosis development.
Methods and Results--Atherosclerosis development was studied in 15 male and 15 female E3L/CRP mice; E3L transgenic littermates were used as controls. The mice were fed a hypercholesterolemic diet to induce atherosclerosis development. Cholesterol exposure did not differ between E3L/CRP and E3L mice. Plasma CRP levels were on average 10.2±6.5 mg/L in male E3L/CRP mice, 0.2±0.1 mg/L in female E3L/CRP mice, and undetectable in E3L mice. Quantification of atherosclerosis showed that lesion area in E3L/CRP mice was not different from that in E3L mice.
Conclusion--This study demonstrates that mildly elevated levels of CRP in plasma do not contribute to the development of early atherosclerosis in hypercholesterolemic E3L/CRP mice.
Key words: atherosclerosis • C-reactive protein • inflammation • mouse • transgene
This article has been cited by other articles:
 |
|
 |
|
  G. D. Norata, P. Marchesi, V. K. Pulakazhi Venu, F. Pasqualini, A. Anselmo, F. Moalli, I. Pizzitola, C. Garlanda, A. Mantovani, and A. L. Catapano Deficiency of the Long Pentraxin PTX3 Promotes Vascular Inflammation and Atherosclerosis Circulation, August 25, 2009; 120(8): 699 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Filep Platelets Affect the Structure and Function of C-Reactive Protein Circ. Res., July 17, 2009; 105(2): 109 - 111. [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Ortiz, G. L. Campana, J. R. Woods, G. Boguslawski, M. J. Sosa, C. L. Walker, and C. A. Labarrere Continuously-Infused Human C-Reactive Protein Is Neither Proatherosclerotic Nor Proinflammatory in Apolipoprotein E-Deficient Mice Experimental Biology and Medicine, June 1, 2009; 234(6): 624 - 631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. B. Grammer, W. Marz, W. Renner, B. O. Bohm, and M. M. Hoffmann C-reactive protein genotypes associated with circulating C-reactive protein but not with angiographic coronary artery disease: the LURIC study Eur. Heart J., January 2, 2009; 30(2): 170 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Welsh, P.H. Whincup, O. Papacosta, S.G. Wannamethee, L. Lennon, A. Thomson, A. Rumley, and G.D.O. Lowe Serum matrix metalloproteinase-9 and coronary heart disease: a prospective study in middle-aged men QJM, October 1, 2008; 101(10): 785 - 791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wu, M. J. Stevenson, J. M. Brown, E. A. Grunz, T. L. Strawn, and W. P. Fay C-Reactive Protein Enhances Tissue Factor Expression by Vascular Smooth Muscle Cells: Mechanisms and In Vivo Significance Arterioscler Thromb Vasc Biol, April 1, 2008; 28(4): 698 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Singh, M. V. Suresh, D. C. Prayther, J. P. Moorman, A. E. Rusinol, and A. Agrawal C-Reactive Protein-Bound Enzymatically Modified Low-Density Lipoprotein Does Not Transform Macrophages into Foam Cells J. Immunol., March 15, 2008; 180(6): 4316 - 4322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Xing, F. G. Hage, Y.-F. Chen, M. A. McCrory, W. Feng, G. A. Skibinski, E. Majid-Hassan, S. Oparil, and A. J. Szalai Exaggerated Neointima Formation in Human C-Reactive Protein Transgenic Mice Is IgG Fc Receptor Type I (Fc{gamma}RI)-Dependent Am. J. Pathol., January 1, 2008; 172(1): 22 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kovacs, P. Tornvall, R. Nilsson, J. Tegner, A. Hamsten, and J. Bjorkegren Human C-reactive protein slows atherosclerosis development in a mouse model with human-like hypercholesterolemia PNAS, August 21, 2007; 104(34): 13768 - 13773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Bisoendial, J. J. P. Kastelein, S. L. M. Peters, J. H. M. Levels, R. Birjmohun, J. I. Rotmans, D. Hartman, J. C. M. Meijers, M. Levi, and E. S. G. Stroes Effects of CRP infusion on endothelial function and coagulation in normocholesterolemic and hypercholesterolemic subjects J. Lipid Res., April 1, 2007; 48(4): 952 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhong, S.-H. Li, S.-M. Liu, P. E. Szmitko, X.-Q. He, P. W.M. Fedak, and S. Verma C-Reactive Protein Upregulates Receptor for Advanced Glycation End Products Expression in Human Endothelial Cells Hypertension, September 1, 2006; 48(3): 504 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P Casas, T. Shah, J. Cooper, E. Hawe, A. D McMahon, D. Gaffney, C. J Packard, D. S O'Reilly, I. Juhan-Vague, J. S Yudkin, et al. Insight into the nature of the CRP-coronary event association using Mendelian randomization Int. J. Epidemiol., August 1, 2006; 35(4): 922 - 931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Scirica, D. A. Morrow, S. Verma, S. Devaraj, I. Jialal, B. M. Scirica, D. A. Morrow, S. Verma, S. Devaraj, and I. Jialal The Verdict Is Still Out Circulation, May 2, 2006; 113(17): 2128 - 2151. [Full Text] [PDF]
|
|
|
|
|
|
M. V. Suresh, S. K. Singh, D. A. Ferguson Jr., and A. Agrawal Role of the Property of C-Reactive Protein to Activate the Classical Pathway of Complement in Protecting Mice from Pneumococcal Infection J. Immunol., April 1, 2006; 176(7): 4369 - 4374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bisoendial, R. Birjmohun, T. Keller, S. van Leuven, H. Levels, M. Levi, J. Kastelein, and E. Stroes Circ. Res., December 9, 2005; 97(12): e115 - e116. [Full Text] [PDF]
|
|
|
|
|
|
J. Torzewski C-Reactive Protein and Atherogenesis: New Insights from Established Animal Models Am. J. Pathol., October 1, 2005; 167(4): 923 - 925. [Full Text] [PDF]
|
|
|
|
|
|
H. Sun, T. Koike, T. Ichikawa, K. Hatakeyama, M. Shiomi, B. Zhang, S. Kitajima, M. Morimoto, T. Watanabe, Y. Asada, et al. C-Reactive Protein in Atherosclerotic Lesions: Its Origin and Pathophysiological Significance Am. J. Pathol., October 1, 2005; 167(4): 1139 - 1148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Singh, S. Devaraj, and I. Jialal C-Reactive Protein Decreases Tissue Plasminogen Activator Activity in Human Aortic Endothelial Cells: Evidence that C-Reactive Protein Is a Procoagulant Arterioscler Thromb Vasc Biol, October 1, 2005; 25(10): 2216 - 2221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T.H. Yeh A New Perspective on the Biology of C-Reactive Protein Circ. Res., September 30, 2005; 97(7): 609 - 611. [Full Text] [PDF]
|
|
|
|
|
|
J. Nilsson CRP--Marker or Maker of Cardiovascular Disease? Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1527 - 1528. [Full Text] [PDF]
|
|