1. A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function
- Author
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Hans-Peter Gerber, Nicholas VanBruggen, Reed Hickey, Yan Huang, Frank J. Giordano, Kirk L. Peterson, Pilar Ruiz-Lozano, Simon-Peter Williams, John Ross, Napoleone Ferrara, Stuart Bunting, Kenneth R. Chien, Anjali K. Nath, Yusu Gu, and Nancy D. Dalton
- Subjects
Vascular Endothelial Growth Factor A ,Cardiac function curve ,medicine.medical_specialty ,Endothelial Growth Factors ,Biology ,Mice ,chemistry.chemical_compound ,Paracrine signalling ,Mediator ,Internal medicine ,medicine ,Animals ,In Situ Hybridization ,Mice, Knockout ,Lymphokines ,Multidisciplinary ,Vascular Endothelial Growth Factors ,Gene Expression Profiling ,Myocardium ,Cardiac myocyte ,Heart ,Biological Sciences ,Immunohistochemistry ,Cardiovascular physiology ,Vascular endothelial growth factor B ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,Endocrinology ,chemistry ,Models, Animal ,cardiovascular system - Abstract
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.
- Published
- 2001
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