Helicobacter pylori down-regulates the receptors of vascular endothelial growth factor and angiopoietin in vascular endothelial cells: implications in the impairment of gastric ulcer healing.

Abstract

Once a peptic ulcer has developed, angiogenesis plays a critical role in its healing by enhancing the microcirculation in the healing site. Previous reports have shown that Helicobacter pylori infection delays the healing of chronic gastric ulcers. To elucidate the mechanism of delayed ulcer healing caused by H. pylori, we investigated the angiogenic phenotype and expression of receptors of angiogenic growth factors in vascular endothelial cells. After human umbilical vein endothelial cells (HUVECs) were treated with H. pylori water extract, angiogenic phenotype was determined by capillary tube formation and DNA synthesis assay. The expressions of the receptors of vascular endothelial growth factor and angiopoietin-1/-2 were assessed by reverse transcription-polymerase chain reaction and Western blot analysis in HUVECs and by double immunofluorescent staining in gastric mucosa. Angiogenic signaling in HUVECs was evaluated by using a quantitative intracellular calcium mobilization assay. H. pylori water extract significantly inhibited capillary tube formation and DNA synthesis and down-regulated the expressions of receptors of vascular endothelial growth factor and angiopoietin in HUVECs. H. pylori water extract suppressed vascular endothelial growth factor-induced intracellular calcium signaling in HUVECs. H. pylori may inhibit the expression of angiogenic growth factor receptors in vascular endothelial cells, which could explain, in part, the delayed healing of gastric ulcer by H. pylori.