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

Abstract

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. (Arterioscler Thromb Vasc Biol. 1998;18:1386-1392.)

Enzymatically Modified Low‐Density Lipoprotein Is Present in All Stages of Aortic Valve Sclerosis: Implications for Pathogenesis of the Disease

“…It is well known, however, that most of the CRP within atherosclerotic lesions derives from plasma CRP insudation 24. We therefore performed extensive immunohistochemical studies using a well‐established mouse monoclonal anti‐CRP antibody 12, 13, 24, 25. Surprisingly, besides increasing extracellular staining around calcified areas of grade 2 to 4 lesions (rather impressive in grade 4 lesions) as well as rare intracellular staining, we were not able to detect any extracellular staining in early lesions (Figure 5B, left panels).…”

C-Reactive Protein, Insulin Resistance, Central Obesity, and Coronary Heart Disease Risk in Indian Asians From the United Kingdom Compared With European Whites

“…This question, in turn, focuses attention on the possibility that CRP itself might contribute to atherothrombosis. CRP selectively binds to LDL, especially the modified LDL found within atherosclerotic plaques, 30 and CRP is present almost universally in the plaques, 31 colocalized with both modified LDL and activated complement. 30 The binding of CRP to ligands, including modified LDL, activates complement and could be pro-inflammatory and contribute to atherogenesis.…”

Relationships of C-reactive protein, uric acid, and glomerular filtration rate to arterial stiffness in Japanese subjects

“…Torzewski et al 30 have reported that CRP deposited in the arterial wall in early atherosclerosis activates a complement protein, which might cause Figure 1 Adjusted means of baPWV compared among quartiles of (a) CRP, (b) UA, and (c) estimated GFR in male subjects (adjusted for age, BMI, systolic blood pressure, HR, TC, HDL, FBS, log TG, UA (except for analysis of the quartile UA), estimated GFR (except for analysis of the quartile estimated GFR), log CRP (except for analysis of the quartile CRP), smoking status, alcohol consumption, frequency of exercise, hyperlipidemia, and diabetes). Figure 2 Adjusted means of baPWV compared among quartiles of (a) CRP, (b) UA, and (c) estimated GFR in female subjects (adjusted for age, BMI, systolic blood pressure, HR, TC, HDL, FBS, log TG, UA (except for analysis of the quartile UA), estimated GFR (except for analysis of the quartile estimated GFR), log CRP (except for analysis of the quartile CRP), smoking status, alcohol consumption, frequency of exercise, hyperlipidemia, diabetes, and menopausal status).…”