Expression of vascular endothelial growth factor and receptor tyrosine kinases in cardiac ischemia/reperfusion injury

Introduction ar 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). s -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). s ed 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. sion 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.