Local Generation of C-Reactive Protein in Diseased Coronary Artery Venous Bypass Grafts and Normal Vascular Tissue

Abstract

Background-Venous coronary artery bypass grafts (CABGs) are prone to accelerated atherosclerosis. In atherosclerotic diseases, serum C-reactive protein (CRP) levels have become an important diagnostic and prognostic marker. The origin of CRP in this setting remains to be elucidated. Methods and Results-Monoclonal anti-CRP identified CRP expression in medial and intimal ␣-actin-positive smooth muscle cells (SMCs) of diseased CABGs with type V and VI lesions and also of native saphenous veins of atherosclerotic individuals. In addition, patent coronary arteries with type IV and V but not with type I through III lesions exhibited intense SMC staining for CRP. Calcified desobliterates of occluded coronary arteries with end-stage disease did not show SMC staining for CRP and were consistently negative for CRP mRNA, as detected by means of real-time polymerase chain reaction. However, CRP mRNA was expressed in 11 of 15 diseased CABGs and also in 10 of 15 native veins. By contrast, only 3 of 18 internal mammary and 4 of 12 radial arteries with virtually no atherosclerosis were positive for CRP mRNA. Conclusions-CRP is produced by SMCs of atherosclerotic lesions with active disease but not in end-stage plaques. The role of CRP constitutively expressed by normal vascular tissue in vein graft disease has yet to be elucidated. Key Words: atherosclerosis Ⅲ inflammation Ⅲ restenosis I n recent years, serum C-reactive protein (CRP) has become a powerful marker of future cardiovascular events. 1,2 CRP is linked to vascular inflammation because it attracts monocytes and mediates LDL uptake by macrophages. 3,4 Furthermore, CRP induces adhesion molecule expression but attenuates NO production of human endothelial cells. 5,6 Histological investigations have described an association between intimal CRP deposition and the development of atherosclerotic plaques. 7,8 None of these studies supposed that CRP immunoreactivity resulted from local expression of CRP. We speculated that elevated serum CRP levels do not reflect continuous hepatic CRP synthesis but rather represent local production. This hypothesis has recently been corroborated by findings of detectable CRP mRNA and protein in postmortem cases of aortosclerotic plaques. 9 Yasojima et al 9 described smooth muscle cells (SMCs) and macrophages as sites of CRP production. These data-together with our observation of CRP production by renal epithelial cells 10 -argue against the liver as the only site of CRP formation. The aim of the present study was to examine local generation of CRP in human atherosclerotic lesions. Because we have been interested for years in the increased reocclusion rate of coronary artery venous bypass grafts (CABGs), 11 we investigated samples of diseased CABGs for CRP mRNA and protein expression. The results were compared with patent atherosclerotic coronary arteries and calcified coronary desobliterates as well as with native saphenous veins, internal mammary arteries (IMAs), and radial arteries (RAs). Methods Sample CollectionFor CRP mRNA detection, 10 d...

Clinical Usefulness of Very High and Very Low Levels of C-Reactive Protein Across the Full Range of Framingham Risk Scores

“…For example, mice transgenic for human CRP not only begin to express elevated CRP levels for the first time but also have increased rates of arterial thrombosis, at least compared with wild-type mice that minimally express CRP. 12 Recent work further indicates that CRP can be produced within the vascular smooth muscle of diseased coronary arteries 13,14 and that this production may directly lead to the expression of several mediators of the atherothrombotic process, including adhesion molecule induction, reduced NO production, and altered fibrinolytic function. 15 Thus, individuals without expressed CRP levels may largely be free of these proatherogenic responses.…”

Comparison of Effects of Rosuvastatin and Atorvastatin on Plaque Regression in Korean Patients With Untreated Intermediate Coronary Stenosis

“…15 Several mechanisms have been described by which CRP and other inflammatory mediators may be actively involved in atherogenesis. 16 CRP is produced by smooth muscle cells of atherosclerotic lesions, 17 and the locally produced CRP could directly participate in atherogenesis and the development of cardiovascular complications. In the present study, plaque was increased in 38% of patients Data are given as mean ± SD or n (%).…”

Thematic review series: The Immune System and Atherogenesis. Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease?

“…However, if these in vitro studies are valid, CRP could be involved at multiple stages of early and late atherosclerosis: endothelial cell injury, impairment of vasodilation, enhanced monocyte adhesion and chemotaxis, lipid accumulation by monocyte-macrophages, smooth muscle cell proliferation, thrombosis, and plaque rupture. Moreover, CRP has been detected immunohistochemically in atherosclerotic lesions (11,64,65).…”