Vegf, flk-1, and flt-1 expression in a rat myocardial infarction model of angiogenesis.. Li, Jian, Lawrence F. Brown[angstrom]a, Mark G. Hibberd, Jessica D. Grossman, James P. Morgan, and Michael Simons. Vascular Biology Unit, Cardiovascular Division, Department of Medicine, and Department of Pathology, Beth Israel Hospital, Harvard Medical School, Boston, MA 02215.
APStracts 2:0422H, 1995.
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 expression of the growth factor and its receptors in a rat infarct model. After an acute MI, we observed an initial rapid (1 hr) 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 LV was later replaced by an increase predominantly limited to peri-MI areas 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 to do so for as late as 6 weeks. 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 VEGF/VEGF receptor system plays an important role in the angiogenesis and stromal deposition associated with myocardial infarction. 

Received 4 August 1995; accepted in final form 11 September 1995.
APS Manuscript Number H735-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95