Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1398-1404
Published online before print June 12, 2003, doi: 10.1161/01.ATV.0000081637.36475.BC
Published online before print June 12, 2003, doi: 10.1161/01.ATV.0000081637.36475.BC
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© 2003 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Interaction of Oxidative Stress and Inflammatory Response in Coronary Plaque Instability
Important Role of C-Reactive Protein
From the Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine (S.K., N.I., K.M, H.A., J.E., K.H., S.K., M.Y.) and Division of Surgical Pathology, Department of Biological Informatics (Y.H., H.Y., H.I.), Kobe University Graduate School of Medicine, and Cardiology Division, Miki City Hospital (Y.O., M.T, T.M., H.F., K.A., K.K.), Japan.
Correspondence to Nobutaka Inoue, MD, PhD, 7-5-1 Kusunoki-cho, chuo-ku, Kobe 650-0017, Japan. E-mail nobutaka{at}med.kobe-u.ac.jp
Objective— C-reactive protein (CRP), a predictor of cardiovascular events, localizes in atherosclerotic arteries and exerts proinflammatory effects on vascular cells. Reactive oxygen species (ROS) have been implicated in atherogenesis and plaque instability.
Methods and Results— Expressional pattern of CRP in directional coronary atherectomy specimens from 39 patients was examined. Characteristics of histological plaque instability and higher levels of serum CRP and fibrinogen were associated with the CRP immunoreactivity. In situ hybridization revealed the presence of CRP mRNA in coronary vasculature. Furthermore, the expression of CRP mRNA and protein was detected in cultured human coronary artery smooth muscle cells (CASMCs) by reverse transcriptase–polymerase chain reaction and Western blotting. In addition, CRP was frequently colocalized with p22phox, an essential component of NADH/NADPH oxidase, which is an important source of ROS in vasculature. Moreover, the incubation of cultured CASMCs with CRP resulted in the enhanced p22phox protein expression and in the generation of intracellular ROS.
Conclusions— The expression of CRP in coronary arteries was associated with histological and clinical features of vulnerable plaque, and it had a prooxidative effect on cultured CASMCs, suggesting that it might play a crucial role in plaque instability and in the pathogenesis of acute coronary syndrome via its prooxidative effect.
Key Words: C-reactive protein • inflammation • oxidative stress • free radicals • coronary artery diseases
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