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

Evelyn C.Nieves Torres, Binxia Yang, Rajiv Janardhanan, Akshaar Brahmbhatt, Edward B Leof, Debabrata Mukhopadhyay, Sanjay Misra

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)e94510
JournalPLoS One
Volume9
Issue number4
DOIs
StatePublished - 2014

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Thrombospondin 1
Thrombospondins
Disintegrins
Adventitia
Lentivirus
fistula
Arteriovenous Fistula
Metalloproteases
metalloproteinases
Small Interfering RNA
Pathologic Constriction
hyperplasia
blood vessels
Hyperplasia
Veins
vascular endothelial growth factor A
Staining and Labeling
gelatinase B
hemodialysis
Matrix Metalloproteinase 9

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Adventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis formation in arteriovenous fistula. / Torres, Evelyn C.Nieves; Yang, Binxia; Janardhanan, Rajiv; Brahmbhatt, Akshaar; Leof, Edward B; Mukhopadhyay, Debabrata; Misra, Sanjay.

In: PLoS One, Vol. 9, No. 4, 2014, p. e94510.

Research output: Contribution to journalArticle

Torres, Evelyn C.Nieves ; Yang, Binxia ; Janardhanan, Rajiv ; Brahmbhatt, Akshaar ; Leof, Edward B ; Mukhopadhyay, Debabrata ; Misra, Sanjay. / Adventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis formation in arteriovenous fistula. In: PLoS One. 2014 ; Vol. 9, No. 4. pp. e94510.
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