Role of 5-lipoxygenase in myocardial ischemia-reperfusion injury in mice

被引:40
作者
Adamek, Anna [1 ]
Jung, Susanne [1 ]
Dienesch, Charlotte [1 ]
Laser, Martin [1 ]
Ertl, Georg [1 ]
Bauersachs, Johann [1 ]
Frantz, Stefan [1 ]
机构
[1] Univ Wurzburg, Med Klin & Poliklin 1, Herz Kreislaufzentrum, D-97080 Wurzburg, Germany
关键词
5-lipoxygenase; leukotriene; ischemia/reperfusion; inflammation;
D O I
10.1016/j.ejphar.2007.05.040
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Myocardial ischemia induces 5-lipoxygenase (LOX) translocation and leukotriene production in the heart. Leukotrienes increase inflammatory responses and could thereby aggravate ischemic injury. However, the role of lipoxygenase and leukotrienes in cardiac ischemia/reperfusion damage has not been well defined. Therefore, we tested the effect of ischemia reperfusion in mice with targeted deletion of 5-lipoxygenase, the enzyme converting arachidonic acid in leukotrienes. 5-LOX deficient (KO) and wild-type (WT) mice underwent 30 min of coronary artery ligation and 24 h of reperfusion in vivo. In mice with equivalent area at risk, infarct size was not significantly different between WT and KO mice (infarct/ area at risk 61.7 +/- 3.9 vs. 55.8 +/- 6.6%, WT vs. KO, P=n.s.). However, neutrophil infiltration as well as tumor necrosis factor expression were increased in 5-lipoxygenase deficient mice. In summary, inhibition of 5-lipoxygenase does not affect cardiac ischemia-reperfusion injury but the post-ischemic inflammatory response. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:51 / 54
页数:4
相关论文
共 24 条
[1]   NAFAZATROM-INDUCED SALVAGE OF ISCHEMIC MYOCARDIUM IN ANESTHETIZED DOGS IS MEDIATED THROUGH INHIBITION OF NEUTROPHIL FUNCTION [J].
BEDNAR, M ;
SMITH, B ;
PINTO, A ;
MULLANE, KM .
CIRCULATION RESEARCH, 1985, 57 (01) :131-141
[2]   INCREASED URINARY LEUKOTRIENE EXCRETION IN PATIENTS WITH CARDIAC ISCHEMIA - INVIVO EVIDENCE FOR 5-LIPOXYGENASE ACTIVATION [J].
CARRY, M ;
KORLEY, V ;
WILLERSON, JT ;
WEIGELT, L ;
FORDHUTCHINSON, AW ;
TAGARI, P .
CIRCULATION, 1992, 85 (01) :230-236
[3]   The cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 ameliorates ischemic acute renal failure [J].
Chatterjee, PK ;
Patel, NSA ;
Cuzzocrea, S ;
Brown, PAJ ;
Stewart, KN ;
Mota-Filipe, H ;
Britti, D ;
Eberhardt, W ;
Pfeilschifter, J ;
Thiemermann, C .
CARDIOVASCULAR RESEARCH, 2004, 61 (03) :630-643
[4]   ROLE OF LEUKOTRIENES REVEALED BY TARGETED DISRUPTION OF THE 5-LIPOXYGENASE GENE [J].
CHEN, XS ;
SHELLER, JR ;
JOHNSON, EN ;
FUNK, CD .
NATURE, 1994, 372 (6502) :179-182
[5]   5-lipoxygenase knockout mice exhibit a resistance to splanchnic artery occlusion shock [J].
Cuzzocrea, S ;
Rossi, A ;
Serraino, I ;
Di Paola, R ;
Dugo, L ;
Genovese, T ;
Caputi, AP ;
Sautebin, L .
SHOCK, 2003, 20 (03) :230-236
[6]   EFFECTS OF NAFAZATROM AND INDOMETHACIN ON EXPERIMENTAL MYOCARDIAL ISCHEMIA IN THE ANESTHETIZED DOG [J].
FIEDLER, VB ;
MARDIN, M .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1985, 7 (05) :983-989
[7]  
FORDHUTCHINSON AW, 1990, CRIT REV IMMUNOL, V10, P1
[8]   The inflammatory response in myocardial infarction [J].
Frangogiannis, NG ;
Smith, CW ;
Entman, ML .
CARDIOVASCULAR RESEARCH, 2002, 53 (01) :31-47
[9]   Repetitive postprandial hyperglycemia increases cardiac ischemia/reperfusion injury:: prevention by the α-glucosidase inhibitor acarbose [J].
Frantz, S ;
Calvillo, L ;
Tillmanns, J ;
Elbing, I ;
Dienesch, C ;
Bischoff, H ;
Ertl, G ;
Bauersachs, J .
FASEB JOURNAL, 2005, 19 (01) :591-+
[10]   Peroxisome proliferator activated-receptor agonism and left ventricular remodeling in mice with chronic myocardial infarction [J].
Frantz, S ;
Hu, K ;
Widder, J ;
Bayer, B ;
Witzel, CC ;
Schmidt, I ;
Galuppo, P ;
Strotmann, J ;
Ertl, G ;
Bauersachs, J .
BRITISH JOURNAL OF PHARMACOLOGY, 2004, 141 (01) :9-14