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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