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Proc Natl Acad Sci U S A. 2001 May 8;98(10):5780-5. Epub 2001 May 1.

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

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Cardiovascular Gene Therapy Program, Department of Medicine, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, Room 336C, New Haven, CT 06520, USA.


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 beta-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.

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