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Introduction:Atherosclerosis is a major contributor to the development of cardiovascular diseases (CVD). Epidemiological studies have suggested an association between Helicobacter pylori(H. pylori)infection and atherosclerosis with undefined mechanisms. Endothelial dysfunction is critical to the development of atherosclerosis and CVD.Hypothesis:H. pyloriinfection impaired endothelial function through exosomes-medicated mechanisms.Methods:Both patients and mouse model with H. pyloriinfection were used to test the hypothesis. Young male and female patients (18-35 years old) with and without H. pyloriinfection were recruited to minimize the chance for potential risk factors for endothelial dysfunction in the study. Endothelium-dependent flow-mediated vasodilatation (FMD) of brachial artery was obtained in the patients and control. Mouse infection models with CagA+H. pylorifrom gastric ulcer patients were created to determine if H. pyloriinfection-induced endothelial dysfunction could be re-produced in animal models.Results:H. pyloriinfection significantly decreased endothelium-dependent FMD in young patients without known cardiovascular risk factors compared to age- and sex-matched healthy volunteers. H. pyloriinfection with CagA+H. pylorisimilarly and significantly attenuated acetylcholine-induced endothelium-dependent aortic relaxation without change in nitroglycerin-induced endothelium-independent vascular relaxation in mice. H. pylorieradication significantly improved endothelium-dependent vasodilation in both patients and mice with H. pyloriinfection. Exosomes from conditioned media of human gastric epithelial cells cultured with CagA+H. pylorior serum exosomes from patients with H. pyloriinfection significantly decreased endothelial functions with decreased migration, proliferation, and tube formation in vitro. Inhibition of exosomes secretion with GW4869 effectively preserved endothelial function in mice with H. pyloriinfection.Conclusions:H. pyloriinfection impaired endothelial function in patients and mice through exosome-medicated mechanisms.The findings indicated that H. pyloriinfection might be a novel risk factor for CVD especially for young patients.