AUTHOR=Zhao Xi , Miao Guolin , Zhang Lijun , Zhang Yuke , Zhao Huanhuan , Xu Zhelong , Wang Beibei , Zhang Lijun 

TITLE=Chlamydia pneumoniae Infection Induces Vascular Smooth Muscle Cell Migration and Atherosclerosis Through Mitochondrial Reactive Oxygen Species-Mediated JunB-Fra-1 Activation

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.879023

DOI=10.3389/fcell.2022.879023

ISSN=2296-634X

ABSTRACT=<p>Infection is closely related to atherosclerosis, which is a major pathological basis for cardiovascular diseases. Vascular smooth muscle cell (VSMC) migration is an important trigger in development of atherosclerosis that is associated with <italic>Chlamydia pneumoniae</italic> (<italic>C. pneumoniae</italic>) infection. However, the mechanism of VSMC migration remains unclear, and whether antioxidant could be a therapeutic target for <italic>C. pneumoniae</italic> infection-induced atherosclerosis also remains unknown. The results showed that <italic>C. pneumoniae</italic> infection mainly impaired mitochondrial function and increased the level of mitochondrial reactive oxygen species (mtROS). The expressions of protein JunB, Fra-1 and Matrix metalloproteinase 2 (MMP) evidently increased after <italic>C. pneumoniae</italic> infection, and the interaction between JunB and Fra-1 was also enhanced. After scavenging mtROS by antioxidant Mito-TEMPO, the increasing expressions of JunB, Fra-1, MMP2 and the capacity of VSMC migration induced by <italic>C. pneumoniae</italic> infection were all inhibited. In comparison with infected ApoE<sup>-/-</sup> mice, the level of ROS in atherosclerotic lesion in ApoE<sup>-/-</sup>TLR2<sup>-/-</sup> mice with <italic>C. pneumoniae</italic> infection decreased. Knocking out TLR2 suppressed the expressions of JunB, Fra-1 and MMP2 in VSMCs and the formation of atherosclerotic lesion after <italic>C. pneumoniae</italic> infection. Furthermore, after using small interfering RNA to inhibit the expression of TLR2, the level of mtROS and the expressions of JunB, Fra-1 and MMP2 apparently decreased. Taken together, <italic>C. pneumoniae</italic> infection may promote VSMC migration and atherosclerosis development by increasing the level of mtROS through TLR2 to activate the JunB-Fra-1/MMP2 signaling pathway. The data provide the first evidence that antioxidant could reduce <italic>C. pneumoniae</italic> infection-induced VSMC migration and atherosclerosis.</p>