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

F J Giordano1, H P Gerber, S P Williams

  • 1Cardiovascular 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

Insights

Cardiac myocytes are crucial for heart function, producing vascular endothelial growth factor (VEGF) essential for blood vessel formation and cardiac development. Deleting VEGF in these cells impairs heart structure and function.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Developmental Biology

Background:

  • The role of cardiac myocytes in paracrine signaling within the heart is not fully understood.
  • Investigating cardiomyocyte-derived secreted factors is crucial for understanding cardiac function and disease.

Purpose of the Study:

  • To elucidate the role of cardiac myocyte-derived vascular endothelial growth factor (VEGF) in cardiac morphogenesis and function.
  • To create a cardiomyocyte-specific knockout model for studying VEGF's impact on the heart.

Main Methods:

  • Generated mice with cardiac myocyte-specific deletion of the vascular endothelial growth factor (VEGF) gene.
  • Analyzed heart structure, microvessel density, contractile function, gene expression, and response to beta-adrenergic stimulation in knockout mice.

Main Results:

  • Cardiac myocyte-specific VEGF deletion resulted in fewer coronary microvessels and thinned ventricular walls.
  • Knockout hearts exhibited depressed basal contractile function and abnormal responses to beta-adrenergic stimulation.
  • Hypoxia-responsive genes involved in energy metabolism were induced in knockout hearts.

Conclusions:

  • Cardiac myocyte-derived VEGF is critical for cardiac morphogenesis and determining heart function.
  • Established an adult murine model of hypovascular, nonnecrotic cardiac contractile dysfunction for further research.

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