High Cholesterol Feeding in C57/Blc6 Mice Alters Expression within The VEGF Receptor-Ligand Family in Corporal Tissue

Authors

  • Donghua Xie MD, PhD,

    1. Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC;
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  • Surovi Hazarika MD, PhD,

    1. Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC;
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  • Amy J. Andrich BS,

    1. Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC;
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  • Mike E. Padgett BS,

    1. Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC;
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  • Christopher D. Kontos MD,

    1. Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC;
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  • Craig F. Donatucci MD,

    1. Department of Surgery, Duke University Medical Center, Durham, NC
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  • Brian H. Annex MD

    Corresponding author
    1. Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC;
      Brian H. Annex, MD, Division of Cardiology, Durham Veterans Affairs and Duke University Medical Center, 508 Fulton St. Box 111A, Durham, NC 27710. Tel: 919-286-0411 ext. 7258; Fax: 919-286-6861; E-mail: annex001@mc.duke.edu
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Brian H. Annex, MD, Division of Cardiology, Durham Veterans Affairs and Duke University Medical Center, 508 Fulton St. Box 111A, Durham, NC 27710. Tel: 919-286-0411 ext. 7258; Fax: 919-286-6861; E-mail: annex001@mc.duke.edu

ABSTRACT

Introduction.  Angiogenesis, the growth and proliferation of blood vessels from existing vascular structures, is mediated by many cytokine growth factors and receptors, among the most important are the vascular endothelial growth factor (VEGF) family.

Aim.  Decreases in VEGF receptor signaling have been linked to abnormalities in vasoreactivity in corporal tissue, but it is unknown if alterations in the VEGF ligands and/or receptors contribute to this process.

Main Outcome Measures.  We sought to determine changes in vasoreactivity and the expression of the family of VEGF ligands and receptors in corporal tissue with cholesterol feeding in C57BL6 mice.

Methods.  Twenty-four mice (N = 8/group) were fed a normal diet (Group 1) or a 1.25% high cholesterol diet for 4 (Group 2) or 12 (Group 3) weeks. Isometric tension studies were performed on corporal strips and dose response curves were generated to evaluate endothelium-dependent and endothelium-independent vasoreactivities. Levels of VEGF-A, B, C, D, VEGF receptors (VEGFRs) were detected by PCR (polymerase chain reaction) and/or western blot/enzyme-linked immunosorbent assay (ELISA). Endothelial and smooth muscle cell contents were determined by immunohistochemistry.

Results.  At 4 weeks there was a small but significant decrease in endothelium-dependent vasoreactivity. Both mRNA and protein levels of VEGFR-1 were decreased, while VEGF-B was increased in Group 2 vs. Group 1, with no change in VEGF-A or endothelial cell content. By 12 weeks, decreases in both endothelium-dependent and endothelium-independent vasoreactivity were evident with decrease in most VEGF ligands (except VEGF-B), receptors, and receptor signaling.

Conclusions.  Cholesterol feeding in C57BL6 mice results in alterations in the VEGF receptor-ligand family that may initially serve to limit the degree of vascular injury but these adaptations fail with the continuation of cholesterol feeding. Xie DH, Hazarika S, Andrich AJ, Padgett ME, Kontos CD, Donatucci CF, and Annex BH. High cholesterol feeding in C57/Blc6 mice alters expression within the VEGF receptor-ligand family in corporal tissue. J Sex Med 2008;5:1137–1148.

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