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

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 () infection. However, the mechanism of VSMC migration remains unclear, and whether antioxidant could be a therapeutic target for infection-induced atherosclerosis also remains unknown. The results showed that 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 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 infection were all inhibited. In comparison with infected ApoE mice, the level of ROS in atherosclerotic lesion in ApoETLR2 mice with infection decreased. Knocking out TLR2 suppressed the expressions of JunB, Fra-1 and MMP2 in VSMCs and the formation of atherosclerotic lesion after 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, 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 infection-induced VSMC migration and atherosclerosis.