As atherosclerosis progressed, the expression of p22phox increased through the vessel wall. p22phox might participate in the pathogenesis and pathophysiology of atherosclerotic coronary disease.

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 p22 phox , 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 p22 phox 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 Ⅲ inflammation Ⅲ oxidative stress Ⅲ free radicals Ⅲ coronary artery diseases A therosclerosis is a chronic inflammatory disease. This concept is supported by recent findings where systemic inflammatory markers such as C-reactive protein (CRP) and fibrinogen are regarded as strong predictors of cardiovascular complications in various clinical settings. [1][2][3] Fibrinogen, a key coagulation factor, is considered to contribute atherogenesis by promoting platelet aggregation, fibrin formation, and plasma viscosity. 4 However, the role of CRP in the pathogenesis of atherosclerotic vascular diseases remains unknown. Recent histological investigations have demonstrated that CRP is present in the human arterial intima at atherosclerotic lesions and is frequently colocalized with the terminal complement complex. 5 Moreover, in vitro studies have shown that the stimulation of human endothelial cells with CRP induces the expression of adhesion molecules and monocyte chemoattractant protein-1 (MCP-1). 6,7 These data suggest that CRP might have direct proinflammatory effects on vascular cells which might, in part, explain the involvement of inflammation in atherogenesis.Reactive oxygen species (ROS) have been implicated in the pathogenesis of a variety of vascular diseases, including atherosclerosis. To date, many types of cells in vasculature have been shown to generate ROS. There are various potential sources that generate ROS in vascular cells: the mitochondrial electron transport chain, cyclooxygenase, lipoxygenase, xanthine oxidase, and NADH/NADPH oxidase. 8,9 Recent ...

No abstract

Objective-NADH/NADPH oxidase is an important source of reactive oxygen species (ROS) in the vasculature. Recently, we demonstrated that p22 phox , an essential component of this oxidase, was expressed in human coronary arteries and that its expression was enhanced with the progression of atherosclerosis. The present study was undertaken to investigate its functional importance in the pathogenesis of coronary artery disease. For this aim, the expression of p22 phox , the distribution of oxidized low density lipoprotein (LDL), and the generation of ROS in directional coronary atherectomy (DCA) specimens were examined. Methods and Results-DCA specimens were obtained from patients with stable or unstable angina pectoris. The distribution of p22 phox and of oxidized LDL was examined by immunohistochemistry. The generation of superoxide in DCA specimens was assessed by the dihydroethidium method and lucigenin-enhanced chemiluminescence. ROS were closely associated with the distribution of p22 phox and oxidized LDL. Not only inflammatory cells but also smooth muscle cells and fibroblasts generated ROS. There was a correlation between ROS and the expression of p22 phox or oxidized LDL. The generation of ROS was significantly higher in unstable angina pectoris compared with stable angina pectoris. Conclusions-ROS generated by p22phox -based NADH/NADPH oxidase likely mediate the oxidative modification of LDL and might play a major role in pathogenesis of atherosclerotic coronary artery disease. (Arterioscler Thromb Vasc Biol.