CagA + Helicobacter pylori , Not CagA - Helicobacter pylori , Infection Impairs Endothelial Function Through Exosomes-Mediated ROS Formation

infection increases the risk for atherosclerosis, and ROS are critical to endothelial dysfunction and atherosclerosis. CagA is a major virulence factor associated with atherosclerosis. The present study aimed to test the hypothesis that CagA effectively colonizes gastric mucosa, and CagA , but not CagA , infection impairs endothelial function through exosomes-mediated ROS formation. C57BL/6 were used to determine the colonization ability of CagA and CagA . ROS production, endothelial function of thoracic aorta and atherosclerosis were measured in CagA and CagA infected mice. Exosomes from CagA and CagA or without infected mouse serum or GES-1 were isolated and co-cultured with bEND.3 and HUVECs to determine how CagA infection impairs endothelial function. Further, GW4869 was used to determine if CagA infection could lead to endothelial dysfunction and atherosclerosis through an exosomes-mediated mechanism. CagA colonized gastric mucosa more effectively than CagA in mice. CagA , not CagA , infection significantly increased aortic ROS production, decreased ACh-induced aortic relaxation, and enhanced early atherosclerosis formation, which were prevented with N-acetylcysteine treatment. Treatment with CagA-containing exosomes significantly increased intracellular ROS production in endothelial cells and impaired their function. Inhibition of exosomes secretion with GW4869 effectively prevented excessive aortic ROS production, endothelial dysfunction, and atherosclerosis in mice with CagA infection. These data suggest that CagA effectively colonizes gastric mucosa, impairs endothelial function, and enhances atherosclerosis exosomes-mediated ROS formation in mice.