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

Abstract

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 <i>Chlamydia pneumoniae</i> (<i>C. pneumoniae</i>) infection. However, the mechanism of VSMC migration remains unclear, and whether antioxidant could be a therapeutic target for <i>C. pneumoniae</i> infection-induced atherosclerosis also remains unknown. The results showed that <i>C. pneumoniae</i> 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 <i>C. pneumoniae</i> 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 <i>C. pneumoniae</i> infection were all inhibited. In comparison with infected ApoE^-/- mice, the level of ROS in atherosclerotic lesion in ApoE^-/-TLR2^-/- mice with <i>C. pneumoniae</i> infection decreased. Knocking out TLR2 suppressed the expressions of JunB, Fra-1 and MMP2 in VSMCs and the formation of atherosclerotic lesion after <i>C. pneumoniae</i> 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, <i>C. pneumoniae</i> 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 <i>C. pneumoniae</i> infection-induced VSMC migration and atherosclerosis.