Abstract 131: Differential Expression of VEGF Isoforms and VEGF Receptors in the Infarcted Heart
Background: VEGF is a family of growth factors that stimulates angiogenesis. It contains four isoforms (VEGF-A, B, C and D), and all members of the VEGF family stimulate cellular responses by binding to VEGF receptors (VEGFR). VEGF-A and B binds to VEGFR-1 and VEGFR-2, while VEGF-C and D bind to VEGFR-3. Following myocardial infarction (MI), angiogenesis occurs and is integral to cardiac repair. Herein, we detected the spatial and temporal expression of VEGF isoforms and VEGF receptor subtypes in the infarcted heart.
Methods and Results: The gene and protein expression of VEGF isoforms and VEGFR subtypes as well as cells expressing VEGF was examined in the infarcted rat heart from day 1 to day 42 postMI. Normal myocardium expressed all VEGF isoforms, and the corresponding cells were primarily endothelial cells. Following MI, VEGF-C and -D gene and protein levels were significantly increased in the infarcted myocardium from day 3 to day 42 and cells expressing VEGF-C and -D were primarily endothelial cells, inflammatory cells and fibroblasts. VEGF-A and -B were significantly reduced in the infarcted myocardium. Similarly, the expression of VEGF-C and -D in the noninfarcted myocardium was significantly increased, and VEGF-A and -B levels were significantly suppressed in the noninfarcted myocardium. VEGFR-3 mRNA and protein levels were significantly increased in the infarcted heart, while cardiac VEGFR-1 and -2 was significantly decreased over 6 weeks of observation.
Conclusions: VEGF isoforms and VEGFR subtypes are differentially expressed in the infarcted heart. Enhanced VEGF-C and -D and their receptors, VEGFR-3, in the infarcted heart indicate the regulatory role of VEGF-C and -D on cardiac angiogenesis during cardiac repair postMI. Suppressed VEGF-A and -B as well as their receptors, VEGFR-1 and -2, suggest that these VEGF isoforms may not be critical in cardiac angiogenesis following MI.
- © 2011 by American Heart Association, Inc.