A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function

FJ Giordano, HP Gerber, SP Williams… - Proceedings of the …, 2001 - National Acad Sciences
FJ Giordano, HP Gerber, SP Williams, N VanBruggen, S Bunting, P Ruiz-Lozano, Y Gu…
Proceedings of the National Academy of Sciences, 2001National Acad Sciences
The role of the cardiac myocyte as a mediator of paracrine signaling in the heart has
remained unclear. To address this issue, we generated mice with cardiac myocyte-specific
deletion of the vascular endothelial growth factor gene, thereby producing a cardiomyocyte-
specific knockout of a secreted factor. The hearts of these mice had fewer coronary
microvessels, thinned ventricular walls, depressed basal contractile function, induction of
hypoxia-responsive genes involved in energy metabolism, and an abnormal response to β …
The role of the cardiac myocyte as a mediator of paracrine signaling in the heart has remained unclear. To address this issue, we generated mice with cardiac myocyte-specific deletion of the vascular endothelial growth factor gene, thereby producing a cardiomyocyte-specific knockout of a secreted factor. The hearts of these mice had fewer coronary microvessels, thinned ventricular walls, depressed basal contractile function, induction of hypoxia-responsive genes involved in energy metabolism, and an abnormal response to β-adrenergic stimulation. These findings establish the critical importance of cardiac myocyte-derived vascular endothelial growth factor in cardiac morphogenesis and determination of heart function. Further, they establish an adult murine model of hypovascular nonnecrotic cardiac contractile dysfunction.
National Acad Sciences