Role of vascular endothelial growth factor in protein loss of Ménétrier's disease

Vascular endothelial growth factor (VEGF) promotes protein leakage from blood vessels and endothelial cell growth. The expression of transforming growth factor (TGF)-alpha and its receptor is increased in the gastric mucosa of patients with Ménétrier's disease. Since TGF-alpha stimulates the expression of VEGF mRNA in cultured keratinocytes, we hypothesized that VEGF may play an important role in the protein leakage of Ménétrier's disease. Immunohistochemistry was performed using specific antibodies against VEGF and CD31 in gastric tissue specimens from 7 patients with Ménétrier's disease and 10 controls. The effect of recombinant TGF-alpha on VEGF production by cultured lamina propria mononuclear cells (LPMCs) was assessed. VEGF expression was detected for LPMCs and occasional epithelial cells of the gastric mucosa of Ménétrier's patients. VEGF-positive LPMCs were increased in tissues from patients with Ménétrier's disease (P<0.001). Of the LPMCs, T-lymphocytes and macrophages were the major sources of VEGF. CD31-positive blood vessels were increased in Ménétrier's tissue. (P<0.05). Recombinant TGF-alpha induced the production of VEGF in cultured LPMCs (P<0.05). In conclusion, the increased expression of VEGF, as a result of overproduction of TGF-alpha, may play a key role in the pathophysiology of Ménétrier's disease.