Growth factor manipulation of intestinal angiogenesis: a possible new paradigm in the management of inflammatory bowel disease.
BACKGROUND
Using the transgenic HLA-B27 rat model of inflammatory bowel disease (IBD), we have previously demonstrated hepatocyte growth factor's (HGF) potential to ameliorate diarrhea and decrease bowel injury. This study was designed to assess the effect of HGF on the neovascularization and inflammation in IBD.


METHODS
Female transgenic HLA-B27 rats were divided into two groups: group 1, saline (control, n = 6); group 2, HGF (150 mug/kg/d, n = 9). Treatments were delivered into the jugular vein via a 14-d subcutaneously placed osmotic mini-pump. Intestinal microvascular density (MVD), histologic inflammatory score, inflammatory cell infiltration, and cytokine expression (tumor necrosis factor-alpha {TNF-alpha}, interferon-gamma {IFN-gamma}, and interleuken-2 {IL-2}) were assessed. Analysis of variance (ANOVA) was used to determine statistical significance.


RESULTS
Administration of HGF resulted in variable but significant alterations in ileal and colonic histology compared with control animals. Compared with group 1, inflammatory cell infiltration was significantly reduced in group 2 (7.7 +/- 1.2 versus 13.3 +/- 2.1 SEM, P < 0.05). Enzyme linked immunosorbent assays (ELISA) demonstrated significantly less expression of ileal IFN-gamma, ileal IL-2 and colonic IL-2 in group 2 (P < 0.05) (Fig. 1). Of importance is that Group 2 exhibited significantly greater MVD in the ileum and colon, both P < 0.05 (Figs. 2 and 3).


CONCLUSIONS
HGF stimulates neovascularization while modulating the intestinal inflammatory response. This is the first demonstration in which a growth factor (HGF) stimulates nonpathologic angiogenesis in an animal model of IBD. HGF administration may be beneficial in the clinical management of IBD.
Thatch
Keith A
KA
St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134, USA.
Mendelson
Kim G
KG
Haber
Marian M
MM
Schwartz
Marshall Z
MZ
D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015796:HLA-B27 Antigen; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000503:physiopathology; D007262:Infusions, Intravenous; D007422:Intestines / Q000098:blood supply / Q000187:drug effects*; D008833:Microcirculation / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D055647:Rats, Transgenic
D043925:Angiogenesis Inducing Agents; D015796:HLA-B27 Antigen; D017228:Hepatocyte Growth Factor