CC chemokine receptor-2 deficiency attenuates oxidative stress and infarct size caused by myocardial ischemia-reperfusion in mice

被引:73
作者
Hayasaki, T
Kaikita, K
Okuma, T
Yamamoto, E
Kuziel, WA
Ogawa, H
Takeya, M
机构
[1] Kumamoto Univ, Grad Sch Med Sci, Dept Cardiovasc Med, Kumamoto 8608556, Japan
[2] Kumamoto Univ, Grad Sch Med Sci, Dept Cell Pathol, Kumamoto 8608556, Japan
[3] Prot Design Labs Inc, Autoimmune & Inflammatory Dis, Fremont, CA USA
关键词
CC chemokine receptor 2; macrophage; metalloproteinases; myocardial infarction; oxidative stress;
D O I
10.1253/circj.70.342
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Monocyte chemoattractant protein-1 (MCP-1) and its major receptor, CC chemokine receptor 2 (CCR2), have been shown to contribute to left ventricular remodeling after myocardial infarction. However, it is unknown whether CCR2 deficiency protects the myocardium after myocardial ischemia-reperfusion. The purpose of the present study was to investigate the effects of CCR2 deficiency on myocardial ischemia-reperfusion injury in mice. Methods and Results Experiments were performed in CCR2(-/-) and wild-type mice subjected to 45 min of ischemia followed by reperfusion. Macrophage infiltration in ischemic lesions was markedly reduced in CCR2(-/-) mice compared with wild-type mice (p<0.01). The infarct size was significantly reduced in CCR2(-/-) mice compared with wild-type mice at 3 days after reperfusion (p<0.001). In situ zymography revealed augmented gelatinolytic activity at 3 days after reperfusion in wild-type mice, but significantly less activity in CCR2(-/-) mice. NADPH oxidase activity, the intensity of nitrotyrosine staining and expression of inducible nitric oxide synthase and thioredoxin-1 were significantly increased in ischemic myocardium in wild-type mice compared with CCR2(-/-) mice, indicating a role for CCR2 in oxidative stress after ischemia-reperfusion. Conclusions Inhibition of the MCP-1/CCR2 pathway may be a useful strategy for attenuating myocardial ischemia-reperfusion injury.
引用
收藏
页码:342 / 351
页数:10
相关论文
共 50 条
[1]   EXPRESSION OF INTERCELLULAR-ADHESION MOLECULE-1 ON RAT CARDIAC MYOCYTES BY MONOCYTE CHEMOATTRACTANT PROTEIN-1 [J].
BAN, K ;
IKEDA, U ;
TAKAHASHI, M ;
KANBE, T ;
KASAHARA, T ;
SHIMADA, K .
CARDIOVASCULAR RESEARCH, 1994, 28 (08) :1258-1262
[2]  
Beckman JS, 1996, AM J PHYSIOL-CELL PH, V271, pC1424
[3]   MYOCARDIAL REPERFUSION, LIMITATION OF INFARCT SIZE, REDUCTION OF LEFT-VENTRICULAR DYSFUNCTION, AND IMPROVED SURVIVAL - SHOULD THE PARADIGM BE EXPANDED [J].
BRAUNWALD, E .
CIRCULATION, 1989, 79 (02) :441-444
[4]  
Carden DL, 2000, J PATHOL, V190, P255, DOI 10.1002/(SICI)1096-9896(200002)190:3<255::AID-PATH526>3.0.CO
[5]  
2-6
[6]   Regulation of superoxide anion production by NADPH oxidase in monocytes/macrophages - Contributions to atherosclerosis [J].
Cathcart, MK .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2004, 24 (01) :23-28
[7]   TGF-β1 attenuates myocardial ischemia-reperfusion injury via inhibition of upregulation of MMP-1 [J].
Chen, HJ ;
Li, DY ;
Saldeen, T ;
Mehta, JL .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2003, 284 (05) :H1612-H1617
[8]   Of mice and dogs: Species-specific differences in the inflammatory response following myocardial infarction [J].
Dewald, O ;
Ren, GF ;
Duerr, GD ;
Zoerlein, M ;
Klemm, C ;
Gersch, C ;
Tincey, S ;
Michael, LH ;
Entman, ML ;
Frangogiannis, NG .
AMERICAN JOURNAL OF PATHOLOGY, 2004, 164 (02) :665-677
[9]   CCL2/monocyte chemoattractant protein-1 regulates inflammatory responses critical to healing myocardial infarcts [J].
Dewald, O ;
Zymek, P ;
Winkelmann, K ;
Koerting, A ;
Ren, GF ;
Abou-Khamis, T ;
Michael, LH ;
Rollins, BJ ;
Entman, ML ;
Frangogiannis, NG .
CIRCULATION RESEARCH, 2005, 96 (08) :881-889
[10]   POSTREPERFUSION INFLAMMATION - A MODEL FOR REACTION TO INJURY IN CARDIOVASCULAR-DISEASE [J].
ENTMAN, ML ;
SMITH, CW .
CARDIOVASCULAR RESEARCH, 1994, 28 (09) :1301-1311