Adventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis formation in arteriovenous fistula.

Hemodialysis vascular access can develop venous neointimal hyperplasia (VNH) causing stenosis. Recent clinical and experimental data has demonstrated that there is increased expression of a disintegrin and metalloproteinase thrombospondin motifs-1 (ADAMTS-1) at site of VNH. The experiments outlined...

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Autores principales: Evelyn C Nieves Torres, Binxia Yang, Bhaskar Roy, Rajiv Janardhanan, Akshaar Brahmbhatt, Ed Leof, Debabrata Mukhopadhyay, Sanjay Misra
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Publicado: Public Library of Science (PLoS) 2014
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spelling oai:doaj.org-article:9ecd8c237195497b9b9e0ddd1738697b2021-11-18T08:23:31ZAdventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis formation in arteriovenous fistula.1932-620310.1371/journal.pone.0094510https://doaj.org/article/9ecd8c237195497b9b9e0ddd1738697b2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24732590/?tool=EBIhttps://doaj.org/toc/1932-6203Hemodialysis vascular access can develop venous neointimal hyperplasia (VNH) causing stenosis. Recent clinical and experimental data has demonstrated that there is increased expression of a disintegrin and metalloproteinase thrombospondin motifs-1 (ADAMTS-1) at site of VNH. The experiments outlined in the present paper were designed to test the hypothesis that targeting of the adventitia of the outflow vein of murine arteriovenous fistula (AVF) using a small hairpin RNA that inhibits ADAMTS-1 expression (LV-shRNA-ADAMTS-1) at the time of fistula creation will decrease VNH. At early time points, ADAMTS-1 expression was significantly decreased associated with a reduction in vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase-9 (MMP-9) (LV-shRNA-ADAMTS-1 transduced vessels vs. controls). These changes in gene and protein expression resulted in favorable vascular remodeling with a significant increase in mean lumen vessel area, decrease in media/adventitia area, with a significant increase in TUNEL staining accompanied with a decrease in cellular proliferation accompanied with a reduction in CD68 staining. Collectively, these results demonstrate that ADAMTS-1 transduced vessels of the outflow vein of AVF have positive vascular remodeling.Evelyn C Nieves TorresBinxia YangBhaskar RoyRajiv JanardhananAkshaar BrahmbhattEd LeofDebabrata MukhopadhyaySanjay MisraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e94510 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Evelyn C Nieves Torres
Binxia Yang
Bhaskar Roy
Rajiv Janardhanan
Akshaar Brahmbhatt
Ed Leof
Debabrata Mukhopadhyay
Sanjay Misra
Adventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis formation in arteriovenous fistula.
description Hemodialysis vascular access can develop venous neointimal hyperplasia (VNH) causing stenosis. Recent clinical and experimental data has demonstrated that there is increased expression of a disintegrin and metalloproteinase thrombospondin motifs-1 (ADAMTS-1) at site of VNH. The experiments outlined in the present paper were designed to test the hypothesis that targeting of the adventitia of the outflow vein of murine arteriovenous fistula (AVF) using a small hairpin RNA that inhibits ADAMTS-1 expression (LV-shRNA-ADAMTS-1) at the time of fistula creation will decrease VNH. At early time points, ADAMTS-1 expression was significantly decreased associated with a reduction in vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase-9 (MMP-9) (LV-shRNA-ADAMTS-1 transduced vessels vs. controls). These changes in gene and protein expression resulted in favorable vascular remodeling with a significant increase in mean lumen vessel area, decrease in media/adventitia area, with a significant increase in TUNEL staining accompanied with a decrease in cellular proliferation accompanied with a reduction in CD68 staining. Collectively, these results demonstrate that ADAMTS-1 transduced vessels of the outflow vein of AVF have positive vascular remodeling.
format article
author Evelyn C Nieves Torres
Binxia Yang
Bhaskar Roy
Rajiv Janardhanan
Akshaar Brahmbhatt
Ed Leof
Debabrata Mukhopadhyay
Sanjay Misra
author_facet Evelyn C Nieves Torres
Binxia Yang
Bhaskar Roy
Rajiv Janardhanan
Akshaar Brahmbhatt
Ed Leof
Debabrata Mukhopadhyay
Sanjay Misra
author_sort Evelyn C Nieves Torres
title Adventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis formation in arteriovenous fistula.
title_short Adventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis formation in arteriovenous fistula.
title_full Adventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis formation in arteriovenous fistula.
title_fullStr Adventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis formation in arteriovenous fistula.
title_full_unstemmed Adventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis formation in arteriovenous fistula.
title_sort adventitial delivery of lentivirus-shrna-adamts-1 reduces venous stenosis formation in arteriovenous fistula.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/9ecd8c237195497b9b9e0ddd1738697b
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