Helicobacter pylori Infection Impairs Endothelial Function Through an Exosome‐Mediated Mechanism
- Resource Type
- Authors
- Duan-Fang Liao; Yuqi Cui; Da Liu; Li Rong; Yixi Li; Xiaoming Liu; Jing-Shu Chi; Hui Wang; Hong Hao; Xiujuan Xia; Tingzi Hu; Huan Li; Yinjie Guo; Canxia Xu; Xue Zhang; Linfang Zhang; Gregory C. Flaker; Zhenguo Liu; Xi-Long Zheng; Jin Cai
- Source
- Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
- Subject
- Helicobacter pylori infection
exosomes
Vascular Medicine
Exosome
endothelial dysfunction
03 medical and health sciences
0302 clinical medicine
Vascular Disease
medicine
cardiovascular risk factor
Endothelial dysfunction
Original Research
030304 developmental biology
0303 health sciences
Helicobacter pylori
biology
Mechanism (biology)
business.industry
bacterial infections and mycoses
Atherosclerosis
medicine.disease
biology.organism_classification
Microvesicles
030220 oncology & carcinogenesis
Immunology
Endothelium/Vascular Type/Nitric Oxide
Cardiology and Cardiovascular Medicine
business
Function (biology)
- Language
- ISSN
- 2047-9980
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.