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Helicobacter pylori infection and endothelial dysfunction

幽门螺杆菌感染与内皮功能障碍

基本信息

批准号：
10252889
负责人：
ZHENGUO LIU
金额：
$ 65.87万
依托单位：
UNIVERSITY OF MISSOURI-COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-15 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10252889
关键词：
Acetylcholine Acute Adult Age Animals Aorta Asia Atherosclerosis Autoimmune Diseases Bacteria Blood Vessels Body Fluids Body mass index Breath Tests C57BL/6 Mouse Cardiovascular Diseases Cardiovascular Physiology Carotid Arteries Carotid Atherosclerotic Disease Cell Communication Cells Cessation of life China Collaborations Coronary Arteriosclerosis Coronary artery Cultured Cells Cytotoxin Data Developed Countries Developing Countries Development Diabetes Mellitus Dilatation - action Endothelial Cells Endothelium Epithelial Epithelial Cells Exhibits Female Functional disorder Gastrointestinal Diseases General Population Genes Gram-Negative Bacteria Helicobacter Infections Helicobacter pylori Hematological Disease Human Hyperlipidemia Hypertension Impairment In Vitro Incidence Infection Injury Ischemic Stroke Lead Lipids Mediating Membrane Lipids MicroRNAs Morbidity - disease rate Multivesicular Body Mus Myocardial Infarction Nitroglycerin Obesity Odds Ratio Pathogenesis Patients Play Population Heterogeneity Prevention Proteins Relaxation Research Personnel Risk Factors Role Serum Smoking Stomach Stroke Structure Testing Tube Ultrasonography Urea Vascular Diseases Vascular Endothelium-Dependent Relaxation Vasodilation Virulence Factors Virulent atherosclerosis risk brachial artery cardiovascular risk factor chronic liver disease design endothelial dysfunction exosome experimental study extracellular vesicles gender difference healthy volunteer improved in vivo infection rate insight male microorganism migration mortality nervous system disorder novel particle prevent sex skin disorder

项目摘要

Abstract Recent studies have suggested an increased risk for atherosclerosis in patients with Helicobacter pylori (H. pylori) infection. However, the mechanism(s) for increased risk for atherosclerosis with H. pylori infection is currently unknown. It is well known that endothelial dysfunction plays a critical role in the development of atherosclerosis and related cardiovascular diseases. The preliminary data for the project have shown that H. pylori infection significantly impairs endothelium-dependent vasodilation in both patients and C57BL/6 mice. Eradication of H. pylori infection in patients and mice significantly improves endothelium-dependent vascular relaxation. Human endothelial cells cultured with serum exosomes from patients with H. pylori infection exhibited significant dysfunction with decreased migration, proliferation, and tube formation in vitro. Exosomes derived from conditioned media of human gastric epithelial cells cultured with H. pylori bacteria containing H. pylori virulent factor cytotoxin-associated gene A (CagA) also significantly decreased endothelial functions similar to serum exosomes. The present project is proposed to test the hypothesis that H. pylori infection impairs endothelial function through exosome-mediated mechanism. The specific aims are: 1) to investigate the effect of H. pylori infection on endothelial function; and 2) to define the role of exosomes in mediating the effect of H. pylori infection on endothelial function. Since the vast majority of patients with H. pylori infection are infected with the bacteria containing the virulence factor CagA, the mice (C57BL/6 mice, both male and female) will be infected with CagA+ H. pylori for the proposed experiments. To determine the effect of CagA protein on endothelial function, CagA- (negative) H. pylori will also be used to repeat the in vitro and in vivo studies for comparison. Endothelial function will be determined in the mice infected with either CagA+ or CagA- H. pylori with PBS as well as inactivated H. pylori as controls. To evaluate the role of exosomes in mediating the effect of H. pylori infection on endothelial function in vivo, the animals will be treated with GW4869 to decrease the release of exosomes from cells. If the hypothesis is true, it is expected that endothelial function will be significantly decreased in the mice infected with either CagA+ or CagA- H. pylori (more so with CagA+ H. pylori if CagA is important to H. pylori infection-induced endothelial dysfunction). Inhibition of exosomes secretion with GW4869 is anticipated to effectively restore endothelial function in mice with H. pylori infection. The data from the proposed study will provide novel insights into the mechanisms for the development of vascular dysfunction in the patients with H. pylori infection, and help explore new and effective strategies to preventing and treating cardiovascular diseases especially atherosclerosis associated with H. pylori infection.