Abstract Body: Background: Helicobacter pylori (H. pylori) infection increases the risk of cardiovascular diseases including atherosclerosis. Endothelial dysfunction is closely associated with atherosclerosis. This study aimed to test the hypothesis that chronic H. pylori infection attenuates endothelial function and promotes atherosclerosis selectively in males.
Methods: Male and age-matched female wildtype C57BL/6 mice and LDL receptor-deficient (LDL^-/-) mice (4 to 6 weeks old) were infected with H. pylori. Mice were fed a regular diet and were euthanized at either 12 or 15 months after H. pylori infection. Aortas were collected from C57BL/6 mice to evaluate endothelial function, and aortas from LDL^-/- mice were evaluated for atherosclerotic burden. Blood pressure, blood glucose and lipid profiles were obtained and analyzed. The presence of H. pylori infection was assessed at the end of the experiment using Rapid Urease Test and Giemsa staining of gastric mucosa.
Results: Over 80% of mice remained infected with H. pylori for up to 15 months. The aortas from male, not female, mice with either 12 or 15 months of H. pylori infection exhibited a significant reduction in acetylcholine-induced endothelium-dependent relaxation, while nitroglycerine-induced endothelium-independent relaxation remained intact. Blood pressure in male, not female, wildtype mice with H. pylori infection for 15 months were also significantly elevated. Similarly, blood glucose levels, non-HDL cholesterol, total cholesterol, and LDL cholesterol were all significantly increased in wildtype male, not female, mice with H. pylori infection. Additionally, aortic atherosclerotic burden was significantly increased in male, not female, LDL^-/- mice with chronic H. pylori infection.
Conclusion: Chronic H. pylori infection induces significant metabolic abnormalities with increased blood glucose and lipid levels, significantly impairs endothelial function, and promotes atherosclerosis selectively in males. These findings suggest that chronic H. pylori infection could significantly contributes to endothelial dysfunction and cardiovascular diseases such as atherosclerosis in males, not females.