Helicobacter pylori Infection Impairs Endothelial Function Through an Exosome‐Mediated Mechanism

Abstract

Background Epidemiological studies have suggested an association between Helicobacter pylori ( H pylori ) infection and atherosclerosis through undefined mechanisms. Endothelial dysfunction is critical to the development of atherosclerosis and related cardiovascular diseases. The present study was designed to test the hypothesis that H pylori infection impaires endothelial function through exosome‐mediated mechanisms. Methods and Results Young male and female patients (18‐35 years old) with and without H pylori infection were recruited to minimize the chance of potential risk factors for endothelial dysfunction for the study. Endothelium‐dependent flow‐mediated vasodilatation of the brachial artery was evaluated in the patients and control subjects. Mouse infection models with CagA + H pylori from a gastric ulcer patient were created to determine if H pylori infection‐induced endothelial dysfunction could be reproduced in animal models. H pylori infection significantly decreased endothelium‐dependent flow‐mediated vasodilatation in young patients and significantly attenuated acetylcholine‐induced endothelium‐dependent aortic relaxation without change in nitroglycerin‐induced endothelium‐independent vascular relaxation in mice. H pylori eradication significantly improved endothelium‐dependent vasodilation in both patients and mice with H pylori infection. Exosomes from conditioned media of human gastric epithelial cells cultured with CagA + H pylori or serum exosomes from patients and mice with H pylori infection significantly decreased endothelial functions with decreased migration, tube formation, and proliferation in vitro. Inhibition of exosome secretion with GW 4869 effectively preserved endothelial function in mice with H pylori infection. Conclusions H pylori infection impaired endothelial function in patients and mice through exosome‐medicated mechanisms. The findings indicated that H pylori infection might be a novel risk factor for cardiovascular diseases.

Helicobacter pylori Infection and Endothelial Dysfunction

“…For the control group, H. pylori infected mice were given the same volume of normal saline. The effectiveness of H. pylori eradication with antimicrobial therapies in mice was confirmed using RUT and Giemsa staining [55,61]. These findings confirm that impairment of endotheliumdependent vasodilation associated with H. pylori infection is reversible in mouse model, similar to the observations in human subjects.…”

“…Indeed, Ach-induced endothelium-dependent relaxation was significantly reduced in mice 1 week after H. pylori infection without Helicobacter pylori Infection and Endothelial Dysfunction DOI: http://dx.doi.org/10.5772/intechopen.97260 change in NTG-induced endothelium-independent relaxation. The impaired Achinduced endothelium-dependent relaxation persisted for as long as the infection was present for at least 24 weeks in the infected mice without change in vascular contraction to either phenylephrine or potassium chloride (Figure 1C), while NTGinduced endothelium-independent relaxation remained intact [55]. These data demonstrated that H. pylori infection selectively impairs endothelium-dependent relaxation, not endothelium-independent relaxation, of thoracic aorta in mice that are similar to the findings in human subjects with H. pylori infection.…”

“…The data showed that patients with H. pylori infection exhibited a significant reduction in endothelium-dependent vasodilatation compared with the controls (Figure 1A). When patients with H. pylori infection were treated with BIS-based quadruple oral anti-H. pylori therapy (100 mg furazolidone, 100 mg doxycycline, 5 mg ilaprazole, and 220 mg colloidal bismuth tartrate, twice a day for 2 weeks) [54], their endothelium-dependent FMD of the brachial artery was effectively restored (Figure 1B) [55]. The effectiveness of H. pylori eradication with antimicrobial therapies was confirmed using 13 C urea breath test for the study patients.…”

A meta‐analysis of the association between Helicobacter pylori infection and risk of atherosclerotic cardiovascular disease

“…Some studies have shown that certain strains of H pylori might lead CVD by binding von Willebrand factor, interacting with GPIb and inducing platelet aggregation 67 . At the same time, H pylori virulence factors CagA, VacA, heat shock protein (HSP) can also play important roles in the occurrence and development of CVD through their own virulence and the induced immune responses 68 . H pylori CagA‐positive strain infection might be involved in coronary atherosclerosis by changing blood lipids, enhancing LDL oxidation, and activating inflammatory responses 69 .…”

The Significance of Exosomal RNAs in the Development, Diagnosis, and Treatment of Gastric Cancer

“…For instance, HP -induced exosomal mesenchymal-epithelial transition factor (MET) can exert a pro-tumorigenic effect on tumor-associated macrophages to promote GC progression [ 42 ]. Another study indicated that exosomes from conditioned media of human gastric epithelial cells are involved in the endothelial function impairment in HP infection [ 43 ]. It is also illustrated that exosomal miRNA-155 derived from HP infection macrophages can immunomodulate the inflammatory response to inhibit the gastritis [ 44 ].…”