Matrix Metalloproteinase-13 in Atherosclerotic Plaque Is Increased by Influenza A Virus Infection

Han Sol Lee, Ji Yun Noh, Ok Sarah Shin, Joon Young Song, Hee Jin Cheong, Woo Joo Kim

Research output: Contribution to journalArticle

Abstract

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 (MMPs) by influenza A virus infection in human cells using quantitative real-time polymerase chain reaction, Western blot, and human MMP-13 enzyme-linked immunosorbent assay. In an animal study, protein expression in the plaque lesions of apolipoprotein E (ApoE)-deficient mice were analyzed by immunohistochemistry and Western blot. RESULTS: We confirmed that MMP-13 was increased in influenza A virus-infected cells. In the aorta of infected ApoE-deficient mice, MMP-13 was increased at 3 days after infection. Immunohistochemical staining results suggested that collagen was degraded in the MMP-13 expression area and that macrophages were the main source of MMP-13 expression. Furthermore, the expression of MMP-13 was regulated by influenza A virus through activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway. CONCLUSIONS: In this study, we demonstrated that p38 MAPK-mediated MMP-13 expression by influenza A virus infection led to destabilization of vulnerable atherosclerotic plaques in the artery.

Original languageEnglish
Pages (from-to)256-266
Number of pages11
JournalThe Journal of infectious diseases
Volume221
Issue number2
DOIs
Publication statusPublished - 2020 Jan 2

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Keywords

  • atherosclerosis
  • influenza A virus
  • matrix metalloproteinase-13
  • p38 mitogen-activated protein kinase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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