Title |
Differential regulation of matrix metalloproteinases in varicella zoster virus-infected human brain vascular adventitial fibroblasts
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Published in |
Journal of the Neurological Sciences, September 2015
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DOI | 10.1016/j.jns.2015.09.349 |
Pubmed ID | |
Authors |
Maria A. Nagel, Alexander Choe, April Rempel, Ann Wyborny, Kurt Stenmark, Don Gilden |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 15 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Other | 4 | 27% |
Student > Ph. D. Student | 3 | 20% |
Student > Bachelor | 1 | 7% |
Student > Master | 1 | 7% |
Researcher | 1 | 7% |
Other | 1 | 7% |
Unknown | 4 | 27% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 3 | 20% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 13% |
Chemistry | 2 | 13% |
Mathematics | 1 | 7% |
Agricultural and Biological Sciences | 1 | 7% |
Other | 1 | 7% |
Unknown | 5 | 33% |