Matrix metalloproteinase-13 in atherosclerotic plaque is increased by influenza A virus infection.

BACKGROUND: Influenza virus infection triggers acute cardiovascular events. Several studies have demonstrated that influenza A virus infection was associated with immune cell influx and increased production of inflammatory cytokines in the atherosclerotic plaque lesion, but the underlying mechanism for these findings is not clear.

METHODS: We examined the expression levels of matrix metalloproteinases by influenza A virus infection in human cells using quantitative RT-PCR, Western blot and human MMP-13 ELISA assay. In an animal study, protein expression in the plaque lesions of ApoE-deficient mice were analyzed by immunohistochemistry and Western blot.

RESULTS: We confirmed that matrix metalloproteinase-13 was increased in influenza A virus-infected cells. In the aorta of infected ApoE-deficient mice, matrix metalloproteinase-13 was increased at 3 days after infection. Immunohistochemical staining results suggested that collagen was degraded in the matrix metalloproteinase-13 expression area and that macrophages were the main source of matrix metalloproteinase-13 expression. Furthermore, the expression of matrix metalloproteinase-13 was regulated by influenza A virus through activation of the p38 MAPK signal pathway.

CONCLUSIONS: In this study, we demonstrated that p38 MAPK-mediated matrix metalloproteinase-13 expression by influenza A virus infection led to destabilization of vulnerable atherosclerotic plaques in artery. (191 words).