Expression of vascular endothelial growth factor and receptor tyrosine kinases in cardiac ischemia/reperfusion injury. |
| |
| Authors: | Manfred Infanger Shideh Faramarzi Jirka Grosse Ekkehard Kurth Claudia Ulbrich Johann Bauer Markus Wehland Reinhold Kreutz Peter Kossmehl Martin Paul Daniela Grimm |
| |
| Institution: | 1. Department of Trauma and Reconstructive Surgery, Charité-Universitätsmedizin Berlin, Benjamin Franklin Campus, 12203 Berlin, Germany;2. Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Benjamin Franklin Campus, 14195 Berlin, Germany;3. Bavarian Animal Health Service, 91522 Ansbach, Germany;4. Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany;1. Heart Institute, Hadassah-Hebrew University Medical Center and Hebrew University Hadassah Medical School, Jerusalem, Israel;2. Institute of Aging Research, Hadassah-Hebrew University Medical Center and Hebrew University Hadassah Medical School, Jerusalem, Israel;3. Department of Geriatrics and Rehabilitation, Hadassah-Hebrew University Medical Center and Hebrew University Hadassah Medical School, Jerusalem, Israel;1. Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark;2. Department of Nuclear Medicine, Herning Regional Hospital, Herning, Denmark;3. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark;1. Mayo Clinic, Rochester, Minnesota;2. Cardiovascular Research Foundation, New York, New York;3. Medical City, Dallas, Texas;4. University of British Columbia and St. Paul''s Hospital, Vancouver, British Columbia, Canada;5. Washington Hospital Center, Washington, District of Columbia;6. Columbia University Medical Center and New York Presbyterian Hospital, New York, New York;7. Cleveland Clinic Foundation, Cleveland, Ohio;8. Emory University, Atlanta, Georgia;1. Julius Wolff Institute and Berlin-Brandenburg School for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Germany;2. Department of Surgery, Hospital Köln-Holweide, Cologne, Germany;3. Department of Orthopaedics and Traumatology, Carl-von-Basedow-Klinikum, Merseburg, Germany;4. Department of Orthopedics, Martin Luther University of Halle-Wittenberg, Halle, Germany |
| |
| Abstract: | INTRODUCTION: 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. CONCLUSION: 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. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
