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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.

Author information

1
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. Frank.Giordano@yale.edu

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 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.

PMID:
11331753
PMCID:
PMC33290
DOI:
10.1073/pnas.091415198
[Indexed for MEDLINE]
Free PMC Article

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