AUTHOR=Wang Na , Zhou Faying , Chen Caiyu , Luo Hao , Guo Jingwen , Wang Wei , Yang Jian , Li Liangpeng 

TITLE=Role of Outer Membrane Vesicles From Helicobacter pylori in Atherosclerosis

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.673993

DOI=10.3389/fcell.2021.673993

ISSN=2296-634X

ABSTRACT=<p>Infection is thought to be involved in the pathogenesis of atherosclerosis. Studies have shown the association between <italic>helicobacter pylori</italic> (<italic>H. pylori</italic>) and coronary artery disease. It is interesting to find <italic>H. pylori</italic> DNA and cytotoxin-associated gene A (CagA) protein in atherosclerotic plaque. Outer membrane vesicles (OMVs), secreted by <italic>H. pylori</italic>, exert effects in the distant organ or tissue. However, whether or not OMVs from <italic>H. pylori</italic> are involved in the pathogenesis of atherosclerosis remains unknown. Our present study found that treatment with OMVs from CagA-positive <italic>H. pylori</italic> accelerated atherosclerosis plaque formation in ApoE<sup>–/–</sup> mice. <italic>H. pylori</italic>-derived OMVs inhibited proliferation and promoted apoptosis of human umbilical vein endothelial cells (HUVECs), which was also reflected in <italic>in vivo</italic> studies. These effects were normalized to some degree after treatment with lipopolysaccharide (LPS)-depleted CagA-positive OMVs or CagA-negative OMVs. Treatment with <italic>H. pylori</italic>-derived OMVs increased reactive oxygen species (ROS) levels and enhanced the activation of nuclear factor-κB (NF-κB) in HUVECs, which were reversed to some degree in the presence of a superoxide dismutase mimetic TEMPOL and a NF-κB inhibitor BAY11-7082. Expressions of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), two inflammatory factors, were augmented after treatment with OMVs from <italic>H. pylori.</italic> These suggest that <italic>H. pylori</italic>-derived OMVs accelerate atherosclerosis plaque formation via endothelium injury. CagA and LPS from <italic>H. pylori</italic>-OMVs, at least in part, participate in these processes, which may be involved with the activation of ROS/NF-κB signaling pathway. These may provide a novel strategy to reduce the incidence and development of atherosclerosis.</p>