C-Reactive Protein Frequently Colocalizes With the Terminal Complement Complex in the Intima of Early Atherosclerotic Lesions of Human Coronary Arteries

From the Department of Cardiology, University of Ulm, Ulm, Germany (J.T., M.F., W.K., J.W., V.H.); the Department of Pathology, Heinrich-Heine-University Düsseldorf, Germany (M.T.); and the Department of Pathology, University of Cambridge, Cambridge, UK (D.E.B., C.F.).

Correspondence to Dr Michael Torzewski, Department of Pathology, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany. E-mail torzewsk{at}mail-rz.uni-duesseldorf.de

Abstract—There is increasing evidence that complement activation may play a role in atherogenesis. Complement proteins have been demonstrated to be present in early atherosclerotic lesions of animals and humans, and cholesterol-induced atherosclerotic lesion formation is reduced in complement-deficient animals. Potential complement activators in atherosclerotic lesions are now a subject matter of debate. C-reactive protein (CRP) is an acute-phase protein that is involved in inflammatory processes in numerous ways. It binds to lipoproteins and activates the complement system via the classic pathway. In this study we have investigated early atherosclerotic lesions of human coronary arteries by means of immunohistochemical staining. We demonstrate here that CRP deposits in the arterial wall in early atherosclerotic lesions with 2 predominant manifestations. First, there is a diffuse rather than a focal deposition in the deep fibroelastic layer and in the fibromuscular layer of the intima adjacent to the media. In this location, CRP frequently colocalizes with the terminal complement complex. Second, the majority of foam cells below the endothelium show positive staining for CRP. In this location, no colocalization with the terminal complement proteins can be observed. Our data suggest that CRP may promote atherosclerotic lesion formation by activating the complement system and being involved in foam cell formation.

Key Words: atherogenesis • C-reactive protein • complement • inflammation

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				J. C. Chambers, S. Eda, P. Bassett, Y. Karim, S. G. Thompson, J. R. Gallimore, M. B. Pepys, and J. S. Kooner C-Reactive Protein, Insulin Resistance, Central Obesity, and Coronary Heart Disease Risk in Indian Asians From the United Kingdom Compared With European Whites Circulation, July 10, 2001; 104(2): 145 - 150. [Abstract] [Full Text] [PDF]

				K. Yasojima, C. Schwab, E. G. McGeer, and P. L. McGeer Complement Components, but Not Complement Inhibitors, Are Upregulated in Atherosclerotic Plaques Arterioscler Thromb Vasc Biol, July 1, 2001; 21(7): 1214 - 1219. [Abstract] [Full Text] [PDF]

				T. P. Zwaka, V. Hombach, and J. Torzewski C-Reactive Protein-Mediated Low Density Lipoprotein Uptake by Macrophages : Implications for Atherosclerosis Circulation, March 6, 2001; 103(9): 1194 - 1197. [Abstract] [Full Text] [PDF]

				K. Yasojima, C. Schwab, E. G. McGeer, and P. L. McGeer Generation of C-Reactive Protein and Complement Components in Atherosclerotic Plaques Am. J. Pathol., March 1, 2001; 158(3): 1039 - 1051. [Abstract] [Full Text] [PDF]

				W. Koenig C-Reactive Protein and Cardiovascular Risk: Has the Time Come for Screening the General Population? Clin. Chem., January 1, 2001; 47(1): 9 - 10. [Full Text] [PDF]

				V. Pasceri, J. T. Willerson, and E. T. H. Yeh Direct Proinflammatory Effect of C-Reactive Protein on Human Endothelial Cells Circulation, October 31, 2000; 102(18): 2165 - 2168. [Abstract] [Full Text] [PDF]

				M. S. Eisenberg, H. J. Chen, M. K. Warshofsky, R. R. Sciacca, H. S. Wasserman, A. Schwartz, and L. E. Rabbani Elevated Levels of Plasma C-Reactive Protein Are Associated With Decreased Graft Survival in Cardiac Transplant Recipients Circulation, October 24, 2000; 102(17): 2100 - 2104. [Abstract] [Full Text] [PDF]

				W. K. Lagrand, C. A. Visser, C. E. Hack, H. W. M. Niessen, R. Nijmeijer, W. Konig, and C. Wanner C-reactive protein and cardiovascular disease: linked by complement? Nephrol. Dial. Transplant., October 1, 2000; 15(10): 1709 - 1710. [Full Text] [PDF]

				M. Torzewski, C. Rist, R. F. Mortensen, T. P. Zwaka, M. Bienek, J. Waltenberger, W. Koenig, G. Schmitz, V. Hombach, and J. Torzewski C-Reactive Protein in the Arterial Intima : Role of C-Reactive Protein Receptor-Dependent Monocyte Recruitment in Atherogenesis Arterioscler Thromb Vasc Biol, September 1, 2000; 20(9): 2094 - 2099. [Abstract] [Full Text] [PDF]

				S A Morre, W Stooker, W K Lagrand, A J C van den Brule, and H W M Niessen Microorganisms in the aetiology of atherosclerosis J. Clin. Pathol., September 1, 2000; 53(9): 647 - 654. [Abstract] [Full Text] [PDF]

				J.C. Kaski, X. Garcia-Moll, W. K. Lagrand, C. A. Visser, H. W. M. Niessen, C. E. Hack, W. T. Hermens, F. W. A. Verheugt, G.-J. Wolbink, and C. E. Hack C-Reactive Protein as a Clinical Marker of Risk Response Circulation, August 29, 2000; 102 (9): e63 - e64. [Full Text] [PDF]