title: Adventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis formation in arteriovenous fistula.
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.
authors.affiliation: Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Evelyn C
authors.initials: EC
authors.lastname: Nieves Torres
authors.affiliation: Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Binxia
authors.initials: B
authors.lastname: Yang
authors.affiliation: Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Roy
authors.affiliation: Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Janardhanan
authors.affiliation: Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Akshaar
authors.initials: A
authors.lastname: Brahmbhatt
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Ed
authors.initials: E
authors.lastname: Leof
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Mukhopadhyay
authors.affiliation: Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States of America; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Misra
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D063194:Adventitia / Q000473:pathology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D017209:Apoptosis; D001164:Arteriovenous Fistula / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D001806:Blood Urea Nitrogen; D049109:Cell Proliferation; D003251:Constriction, Pathologic; D003404:Creatinine / Q000097:blood; D018014:Gene Transfer Techniques; D016086:Lentivirus / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D009392:Nephrectomy; D034741:RNA, Small Interfering / Q000378:metabolism*; D013194:Staining and Labeling; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D066253:Vascular Remodeling; D000097382:CD68 Molecule
chemical_list: D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003404:Creatinine; D020780:Matrix Metalloproteinase 9; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C486323:Adamts1 protein, mouse
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