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Aprotinin Exerts Inhibition of Gene Activation following Myocardial Ischemia and Reperfusion in Rats
Author(s) -
Buerke Michael,
Sankat Dennis,
Schlitt Axel,
Carter Justin,
Werdan Karl,
Buerke Ute
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1146-c
Subject(s) - aprotinin , reperfusion injury , ischemia , medicine , pharmacology , gene expression , myeloperoxidase , inflammation , immunology , gene , chemistry , biochemistry
Reperfusion of ischemic myocardium has been largely attributed to neutrophil infiltration with subsequent endothelial dysfunction, complement activation, cytokine release and cardiac apoptosis. Inhibition of serine proteases with aportinin has been shown to exert cardioprotective effects. In this regard, we analyzed the effect of Aprotinin (Apro) in a rat model of myocardial ischemia and reperfusion (I.e., 20min + 24hours) on gene expression. Apro (20.000U/kg) administered 5 min prior to reperfusion significantly attenuated myocardial injury compared to vehicle treated rats (p<0.01). Further, cardiac myeloperoxidase activity, a marker for neutrophil accumulation was significantly reduced following Apro treatment (p<0.01). Further, analysis of differential gene expression was performed with labeled cDNA obtained from hearts following ischemia and reperfusion of vehicle or Apro treated animals (Atlas™ Rat cDNA Expression Array, Clontech). Ischemia and reperfusion resulted in expression of pro‐inflammatory genes like P‐selectin, MEK 2, JNK, STAT‐3, N‐myc, and c‐jun as well as anti‐inflammatory genes like MIF and MIP. Administration of Apro prior to reperfusion resulted in reduced expression of inflammatory genes as well as in enhanced expression of anti‐inflammatory genes like heat shock protein 27, 60, and 70. When we performed protein analysis we were able to dermine reduced expression of p53, ICAM‐1, p‐selectin, IL‐6, and TNF‐alpha Thus, Apro appears to be an effective means to preserve ischemic myocardium from reperfusion injury due to reduced expression of pro‐inflammatory genes even following 24 hours of reperfusion.