Journal article
Differential regulation of matrix metalloproteinases in varicella zoster virus-infected human brain vascular adventitial fibroblasts
Journal of the neurological sciences, Vol.358(1-2), pp.444-446
11/15/2015
DOI: 10.1016/j.jns.2015.09.349
PMCID: PMC4628845
PMID: 26443282
Abstract
Upon reactivation, varicella zoster virus (VZV) spreads transaxonally, infects cerebral arteries and causes ischemic or hemorrhagic stroke, as well as aneurysms. The mechanism(s) of VZV-induced aneurysm formation is unknown. However, matrix metalloproteinases (MMPs), which digest extracellular structural proteins in the artery wall, play a role in cerebral and aortic artery aneurysm formation and rupture. Here, we examined the effect of VZV infection on expression of MMP-1, -2, -3, and -9 in primary human brain vascular adventitial fibroblasts (BRAFS). At 6days post-infection, VZV- and mock-infected BRAFs were analyzed for mRNA levels of MMP-1, -2, -3 and -9 by RT-PCR and for corresponding total intra- and extracellular protein levels by multiplex ELISA. The activity of MMP-1 was also measured in a substrate cleavage assay. Compared to mock-infected BRAFs, MMP-1, MMP-3 and MMP-9 transcripts, cell lysate protein and conditioned supernatant protein were all increased in VZV-infected BRAFs, whereas MMP-2 transcripts, cell lysate protein and conditioned supernatant protein were decreased. MMP-1 from the conditioned supernatant of VZV-infected BRAFs showed increased cleavage activity on an MMP-1-specific substrate compared to mock-infected BRAFs. Differential regulation of MMPs in VZV-infected BRAFs may contribute to aneurysm formation in VZV vasculopathy.
•VZV infection of cerebral arteries can cause aneurysm and stroke.•MMP-1, -3 and -9 increased and MMP-2 decreased in VZV-infected adventitial cells.•VZV-induced regulation of MMP expression can contribute to aneurysm formation.
Details
- Title: Subtitle
- Differential regulation of matrix metalloproteinases in varicella zoster virus-infected human brain vascular adventitial fibroblasts
- Creators
- Maria A. Nagel - University of Colorado DenverAlexander Choe - University of Colorado DenverApril Rempel - University of Colorado DenverAnn Wyborny - University of Colorado DenverKurt Stenmark - University of Colorado DenverDon Gilden - University of Colorado Denver
- Resource Type
- Journal article
- Publication Details
- Journal of the neurological sciences, Vol.358(1-2), pp.444-446
- DOI
- 10.1016/j.jns.2015.09.349
- PMID
- 26443282
- PMCID
- PMC4628845
- NLM abbreviation
- J Neurol Sci
- ISSN
- 0022-510X
- eISSN
- 1878-5883
- Publisher
- Elsevier B.V
- Number of pages
- 3
- Language
- English
- Date published
- 11/15/2015
- Academic Unit
- Neurology
- Record Identifier
- 9984826360402771
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