Author(s): Li J, Brown LF, Hibberd MG, Grossman JD, Morgan JP,
Abstract Share this page
Abstract Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen that is thought to function by interacting with two high-affinity receptors, flk-1 and flt-1. In an adult heart, angiogenesis can occur in a number of pathological conditions, including atherosclerosis, hypertrophy, and infarction. To determine the role played by VEGF, flk-1, and flt-1 in this process in vivo, we studied the expression of the growth factor and its receptors in a rat infarct model. After an acute myocardial infarction, we observed an initial rapid (1h) rise in VEGF (275\%), flk-1 (375\%), and flt-1 (400\%) mRNA expression throughout the entire heart. Initial diffuse induction of VEGF, flk-1, and flt-1 expression in the left ventricle was later replaced by an increase predominantly limited to perimyocardial infarction area where angiogenesis was taking place. In situ hybridization showed at 6 h after infarction, viable myocytes adjacent to the infarct zone expressed markedly increased amounts of VEGF. At both 6 and 24 h, microvessels at the infarct edge overexpressed both flk-1 and flt-1 mRNAs; at 3 and 7 days new vessels infiltrating the infarct also overexpressed both receptors and continued for as late as 6 wk. In summary, acute myocardial infarction is accompanied by rapid and prolonged increase in expression of VEGF and its receptors with characteristic spatial and temporal kinetic. These findings suggest that the VEGF/VEGF receptor system plays an important role in the angiogenesis and stromal deposition associated with myocardial infarction.
This article was published in Am J Physiol
and referenced in Journal of Autacoids and Hormones