title: A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function.
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.
authors.affiliation: 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
authors.forename: F J
authors.initials: FJ
authors.lastname: Giordano
authors.forename: H P
authors.initials: HP
authors.lastname: Gerber
authors.forename: S P
authors.initials: SP
authors.lastname: Williams
authors.forename: N
authors.initials: N
authors.lastname: VanBruggen
authors.forename: S
authors.initials: S
authors.lastname: Bunting
authors.forename: P
authors.initials: P
authors.lastname: Ruiz-Lozano
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.forename: A K
authors.initials: AK
authors.lastname: Nath
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.forename: R
authors.initials: R
authors.lastname: Hickey
authors.forename: N
authors.initials: N
authors.lastname: Dalton
authors.forename: K L
authors.initials: KL
authors.lastname: Peterson
authors.forename: J
authors.initials: J
authors.lastname: Ross
authors.forename: K R
authors.initials: KR
authors.lastname: Chien
authors.forename: N
authors.initials: N
authors.lastname: Ferrara
mesh_terms: D000818:Animals; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006321:Heart / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors