Interaction of oxidative stress and inflammatory response in coronary plaque instability: important role of C-reactive protein.
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.


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.
Kobayashi
Seiichi
S
Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.
Inoue
Nobutaka
N
Ohashi
Yoshitaka
Y
Terashima
Mitsuyoshi
M
Matsui
Kiyoko
K
Mori
Takao
T
Fujita
Hideki
H
Awano
Kojiro
K
Kobayashi
Katsuya
K
Azumi
Hiroshi
H
Ejiri
Junya
J
Hirata
Ken-ichi
K
Kawashima
Seinosuke
S
Hayashi
Yoshitake
Y
Yokozaki
Hiroshi
H
Itoh
Hiroshi
H
Yokoyama
Mitsuhiro
M
D001167:Arteritis / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism*; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D026901:Membrane Transport Proteins; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009243:NAD / Q000378:metabolism; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000032:analysis; D015854:Up-Regulation
D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D009243:NAD; D005340:Fibrinogen; D002097:C-Reactive Protein; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase