Open AccessA cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function
Author(s) -
Frank J. Giordano,
HansPeter Gerber,
SimonPeter Williams,
Nicholas VanBruggen,
Stuart Bunting,
Pilar RuizLozano,
Yusu Gu,
Anjali K. Nath,
Yan Huang,
Reed Hickey,
Nancy D. Dalton,
Kirk L. Peterson,
John Ross,
Kenneth R. Chien,
Napoleone Ferrara
Publication year - 2001
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.091415198
Subject(s) - cardiac myocyte , paracrine signalling , myocyte , medicine , cardiac function curve , mediator , endocrinology , biology , microbiology and biotechnology , heart failure , receptor
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.