Summary auto-generated
This study investigates how Helicobacter pylori directly damages vascular endothelial cells, which may explain delayed gastric ulcer healing during infection. Researchers treated human umbilical vein endothelial cells (HUVECs) with water extracts from two H. pylori strains differing in virulence factors cagA and vacA. The H. pylori extracts significantly inhibited HUVEC proliferation in a dose-dependent manner, while E. coli extracts had no effect. H. pylori extracts also induced apoptosis in HUVECs through a mitochondrial pathway. Molecular analysis revealed that while total p53 protein levels remained unchanged, phosphorylated p53 increased following H. pylori exposure. Correspondingly, mRNA expression of p21 and Bax—proteins involved in cell cycle arrest and apoptosis—was elevated. These effects occurred independently of cagA and vacA status, suggesting involvement of unidentified H. pylori secreted proteins. The findings suggest that H. pylori directly damages endothelial cells by inhibiting proliferation and triggering apoptosis via p53 phosphorylation and mitochondrial injury, potentially contributing to impaired angiogenesis and delayed ulcer healing in infected patients.
Key findings
- H. pylori water extracts inhibited endothelial cell proliferation dose-dependently, an effect specific to H. pylori and independent of cagA/vacA virulence factors
- H. pylori induced apoptosis in endothelial cells through a mitochondrial pathway involving Bax upregulation
- Phosphorylated p53 protein levels increased following H. pylori exposure, correlating with elevated p21 and Bax mRNA expression
- E. coli extracts did not affect endothelial cell proliferation or apoptosis, demonstrating H. pylori-specific effects
- These endothelial cell effects may contribute to delayed gastric ulcer healing by impairing angiogenesis and microcirculation
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Abstract
Microcirculation plays a crucial role in mucosal physiological function as well as repair of gastric mucosal damage. Endothelial cell damage is known to disturb microcirculation and suppress angiogenesis. Therefore, the direct effect of Helicobacter pylori on endothelial cells in vitro was investigated with H. pylori water extract. The effect of H. pylori water extract on cell proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) was evaluated. The ratio of BrdU-positive HUVECs in both cagA/vacA-positive and -negative H. pylori water extract-treated groups was significantly lower at 24 h than that in the control group, but Escherichia coli water extract did not affect the proliferation of these endothelial cells. Apoptosis was induced by H. pylori water extracts after incubation for 24 h in a cagA/vacA-independent manner. In the mitochondrial permeability transition assay, tetramethylrhodamine methyl ester was accumulated in mitochondria of HUVECs. Western blot analysis showed no difference in the level of total p53 protein in H. pylori water extract-treated and non-treated cells, but the level of phosphorylated p53 protein was increased in the treated cells at 15 and 60 min after addition of the extract. Reverse transcription (RT)-PCR products for p21 and Bax were elevated in the H. pylori water extract-treated cells. p21 levels began to increase 0.51 h after addition of the extract, whereas Bax increased in the period 0.52 h. H. pylori induced a disturbance of cell proliferation and apoptosis in the vascular endothelial cells which may contribute to gastric mucosal injury and to delayed healing of gastric lesions.