title: Angiogenesis-independent cardioprotection in FGF-1 transgenic mice.
abstract: OBJECTIVE
  This study was performed to evaluate the cardioprotective role of acidic fibroblast growth factor-1 (FGF-1) in transgenic mice with cardiac-specific overexpression of human FGF-1.
  
  
  METHODS
  Mice were subjected to coronary artery occlusion for 15-75 min with a continuously recorded 3-lead electrocardiogram (ECG). Infarct size was measured and ERK-1 and -2 activity was assessed by Western blot analysis. Creatine kinase and lactate dehydrogenase activity as marker for cell viability were measured in isolated ventricular myocytes subjected to simulated ischemia.
  
  
  RESULTS
  Infarct development was markedly delayed in transgenics with first signs of myocardial infarction visible at 45 min after coronary artery occlusion compared to 15 min in wildtype. Maximal infarct size (60% of risk area) did not differ, but transgenics reached maximal infarction after 75 min compared to 45 min in wildtype animals. ECG revealed delayed Q-wave development and delayed ST-segment elevation in transgenics. Creatine kinase and lactate dehydrogenase release was significantly attenuated from isolated transgenic myocytes at 4 and 8 h after simulated ischemia. The delay in infarct development is partially due to a constitutive higher expression of the extracellular signal-regulated kinases ERK-1 and -2 in the myocardium of transgenics. Additionally, injection of the ERK-1/2 inhibitor UO126 decreased the cardioprotective effect of FGF-1.
  
  
  CONCLUSIONS
  Cardiac specific overexpression of FGF-1 provides cardioprotection at the level of the cardiac myocyte, independent from angiogenesis, and at least partially mediated via activation of the mitogen activated protein kinase (MAP) ERK-1 and -2.
authors.affiliation: Department of Experimental Cardiology, Max-Planck-Institute, D-61231 Bad Nauheim, Germany. r.zimmer@vascular-genomics.de
authors.forename: Alexandra
authors.initials: A
authors.lastname: Buehler
authors.forename: Alessandra
authors.initials: A
authors.lastname: Martire
authors.forename: Claudia
authors.initials: C
authors.lastname: Strohm
authors.forename: Swen
authors.initials: S
authors.lastname: Wolfram
authors.forename: Borja
authors.initials: B
authors.lastname: Fernandez
authors.forename: Meindert
authors.initials: M
authors.lastname: Palmen
authors.forename: Xander H T
authors.initials: XH
authors.lastname: Wehrens
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Franz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schaper
authors.forename: René
authors.initials: R
authors.lastname: Zimmermann
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D004562:Electrocardiography; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016220:Fibroblast Growth Factor 1 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006439:Hemodynamics / Q000187:drug effects; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D016220:Fibroblast Growth Factor 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases