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

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J Infect Dis. 2019 Nov 6. pii: jiz580. doi: 10.1093/infdis/jiz580. [Epub ahead of print] Matrix metalloproteinase-13 in atherosclerotic plaque is increased by influenza A virus infection.

Lee HS^1,2, Noh JY², Shin OS³, Song JY², Cheong HJ², Kim WJ^1,2.
Author information

1 BK21 Plus Graduate Program Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea (HS.L, WJ.K). 2 Division of Infectious Diseases, Department of Internal Medicine, Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea (HS.L, JY.N, JY.S, HJ.C, WJ.K). 3 Department of Biomedical Sciences, Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea (OS. S).

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 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).
? The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.


KEYWORDS:

Atherosclerosis; Influenza A virus; Matrix Metalloproteinase-13; p38 Mitogen-Activated Protein Kinase

PMID: 31693113 DOI: 10.1093/infdis/jiz580