title: Expression of vascular endothelial growth factor and receptor tyrosine kinases in cardiac ischemia/reperfusion injury.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) expression is regulated by hypoxia and cytokines, including insulin-like growth factor (IGF)-1. We examined the influence of ischemia/reperfusion (I/R) on IGF-1, VEGF, fetal liver kinase (flk-1), fms-like tyrosine kinase-1 (flt-1), and laminin using an isolated hemoperfused working porcine heart model of acute ischemia (2 h) and reperfusion (4 h).
  
  
  METHODS
  Twenty-three porcine hearts were randomized into the following groups: five nonischemic control hearts (Group C), five I/R hearts with occlusion of the ramus circumflexus; three I/R hearts treated with quinaprilat, a potent angiotensin-converting enzyme (ACE) inhibitor (Group Q); five I/R hearts treated with angiotensin I (Group Ang I), and 5 I/R hearts treated with Ang I and quinaprilat (Group QA).
  
  
  RESULTS
  Compared to C, VEGF mRNA and protein contents were significantly increased in I/R and Ang I hearts. flk-1 and flt-1 were increased in I/R (2.2-/1.95-fold) and further elevated by Ang I (3.2-/3.4-fold) compared with C. Quinaprilat application attenuated the amount of VEGF significantly and of flk-1 slightly but not that of flt-1. In contrast, IGF-1 and IGF-1 receptor (IGF-1R) proteins were elevated in I/R hearts (3-/1.4-fold vs. C) and further increased in the presence of Q. These findings were accompanied by an elevation of laminin mRNA and protein levels. Moreover, we observed an increase in collagen Type IV and chondroitin sulfate content in I/R (2.9-/1.4-fold) and Ang I (3.5-/1.5-fold) hearts. Quinaprilat significantly reduced laminin and chondroitin sulfate proteins.
  
  
  CONCLUSIONS
  These data suggest that the VEGF/VEGF receptor and IGF-1-IGF-1R systems are activated by I/R. The benefits of ACE inhibition in attenuation of cardiac remodeling may be mediated by IGF-1.
authors.affiliation: Department of Trauma and Reconstructive Surgery, Charité-Universitätsmedizin Berlin, Benjamin Franklin Campus, 12203, Berlin, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Infanger
authors.forename: Shideh
authors.initials: S
authors.lastname: Faramarzi
authors.forename: Jirka
authors.initials: J
authors.lastname: Grosse
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Kurth
authors.forename: Claudia
authors.initials: C
authors.lastname: Ulbrich
authors.forename: Johann
authors.initials: J
authors.lastname: Bauer
authors.forename: Markus
authors.initials: M
authors.lastname: Wehland
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
authors.forename: Peter
authors.initials: P
authors.lastname: Kossmehl
authors.forename: Martin
authors.initials: M
authors.lastname: Paul
authors.forename: Daniela
authors.initials: D
authors.lastname: Grimm
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002809:Chondroitin Sulfates / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D013552:Swine; D044005:Tetrahydroisoquinolines / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D024141:Collagen Type IV; D007797:Laminin; D012333:RNA, Messenger; D044005:Tetrahydroisoquinolines; D042461:Vascular Endothelial Growth Factor A; C054501:quinaprilat; D007334:Insulin-Like Growth Factor I; D002809:Chondroitin Sulfates; D000803:Angiotensin I; D020794:Receptor Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2