<i>Helicobacter pylori</i> Infection Impairs Endothelial Function Through an Exosome‐Mediated Mechanism

Abstract

Background Epidemiological studies have suggested an association between <i>Helicobacter pylori</i> (<i>H pylori</i>) 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 <i>H pylori</i> infection impaires endothelial function through exosome-mediated mechanisms. Methods and Results Young male and female patients (18-35 years old) with and without <i>H pylori</i> 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⁺<i>H pylori</i> from a gastric ulcer patient were created to determine if <i>H pylori</i> infection-induced endothelial dysfunction could be reproduced in animal models. <i>H pylori</i> 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. <i>H pylori</i> eradication significantly improved endothelium-dependent vasodilation in both patients and mice with <i>H pylori</i> infection. Exosomes from conditioned media of human gastric epithelial cells cultured with CagA⁺<i>H pylori</i> or serum exosomes from patients and mice with <i>H pylori</i> infection significantly decreased endothelial functions with decreased migration, tube formation, and proliferation in vitro. Inhibition of exosome secretion with GW4869 effectively preserved endothelial function in mice with <i>H pylori</i> infection. Conclusions <i>H pylori</i> infection impaired endothelial function in patients and mice through exosome-medicated mechanisms. The findings indicated that <i>H pylori</i> infection might be a novel risk factor for cardiovascular diseases.