High cholesterol feeding in C57/Blc6 mice alters expression within the VEGF
receptor-ligand family in corporal tissue.
Authors Xie D, Hazarika S, Andrich AJ, Padgett ME, Kontos CD, Donatucci CF, Annex BH
Submitted By Thomas Coffman on 8/11/2010
Status Published
Journal The journal of sexual medicine
Year 2008
Date Published 5/1/2008
Volume : Pages 5 : 1137 - 1148
PubMed Reference 18439153
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.

Investigators with authorship
Thomas CoffmanDuke University Medical Center