J. A. Shepherd1, P. J. Matheson1, J. W. Smith1, R. N. Garrison1, C. D. Downard1 1University Of Louisville,Department Of Surgery,Louisville, KY, USA
Introduction:
Necrotizing enterocolitis (NEC) alters ileal blood flow via dysregulation of mediators of vascular tone, but deranged intestinal angiogenesis might also contribute to impaired perfusion. Vascular endothelial growth factor receptor 2 (VEGFR-2) may have an important role in neonatal intestinal vascular development and control. We hypothesized that the gene and protein dysregulation that occurs during experimental NEC results in altered VEGFR-2 protein expression.
Methods:
Sprague-Dawley rats were randomly separated into NEC and CONTROL groups by litter. NEC groups were delivered by C-section 12 hrs prematurely, formula fed, exposed to intermittent cold and hypoxia, and given a single oral dose of lipopolysaccharide (n=95). CONTROLs were delivered vaginally and dam-fed. Ileum samples were obtained at 0, 12, 24, 48, 72 and 96 hours of life and Western blots were performed with antibodies against VEGFR-2 and β -actin for normalization by individual animal. Statistical analysis was performed using 2-way ANOVA and a priori P<0.05.
Results:
In NEC animals, ileal VEGFR-2 levels increase markedly from the 0 time point, peaking at 24 hours, before returning to baseline levels at 96 hours of life (see Figure 1). In the CONTROL animals, ileal VEGFR-2 concentration was significantly lower than in NEC animals until 96 hours of life.
Conclusion:
VEGFR-2 is the major signaling receptor for VEGFA, the vasoactive form of VEGF. In this experimental model of NEC, VEGFR-2 expression is increased in NEC compared to CONTROL animals, suggesting dysfunction in this intestinal microvascular angiogenesis pathway. When coupled with alterations in VEGFA levels in NEC, this could provide an explanation for vascular dysfunction and poor intestinal perfusion in NEC.
