The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation

Rajiv Janardhanan, Binxia Yang, Sreenivasulu Kilari, Edward B Leof, Debabrata Mukhopadhyay, Sanjay Misra

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: To determine if a second dose of a lentivirus mediated small hairpin RNA that inhibits Vegf-A gene expression (LV-shRNA-Vegf-A) can improve lumen vessel area (LVA) of the outflow vein of an arteriovenous fistula (AVF) and decrease venous neointimal hyperplasia. Materials and Methods: Chronic kidney disease was created in C57BL/6 mice; 28 days later, an AVF was created by connecting the right carotid artery to the ipsilateral jugular vein. Immediately after AVF creation, 5 × 106 plaque-forming units of LV-shRNA-Vegf-A or control shRNA was administered to the adventitia of the outflow vein, and a second dose of the same treatment was administered 14 days later. Animals were sacrificed at 21 days, 28 days, and 42 days after AVF creation for reverse transcription polymerase chain reaction and histomorphometric analyses. Results: By day 21, there was a 125% increase in the average LVA (day 21, P = .11), with a decrease in cell proliferation (day 21, P = .0079; day 28, P = .28; day 42, P = .5), decrease in α-smooth muscle cell actin staining (day 21, P <.0001; day 28, P <.05; day 42, P = .59), and decrease in hypoxic stress (day 21, P <.001; day 28, P = .28; day 42, P = .46) in LV versus control shRNA vessels. Conclusions: A second dose of LV-shRNA-Vegf-A administration results in a moderate improvement in LVA at day 21.

Original languageEnglish (US)
JournalJournal of Vascular and Interventional Radiology
DOIs
StateAccepted/In press - Jun 30 2015

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Adventitia
Lentivirus
Arteriovenous Fistula
Vascular Endothelial Growth Factor A
Small Interfering RNA
Pathologic Constriction
Veins
Jugular Veins
Chronic Renal Insufficiency
Inbred C57BL Mouse
Carotid Arteries
Reverse Transcription
Smooth Muscle Myocytes
Hyperplasia
Actins
Cell Proliferation
Staining and Labeling
Gene Expression
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

@article{8607761948a449bf8f3bd9223d7c6e98,
title = "The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation",
abstract = "Purpose: To determine if a second dose of a lentivirus mediated small hairpin RNA that inhibits Vegf-A gene expression (LV-shRNA-Vegf-A) can improve lumen vessel area (LVA) of the outflow vein of an arteriovenous fistula (AVF) and decrease venous neointimal hyperplasia. Materials and Methods: Chronic kidney disease was created in C57BL/6 mice; 28 days later, an AVF was created by connecting the right carotid artery to the ipsilateral jugular vein. Immediately after AVF creation, 5 × 106 plaque-forming units of LV-shRNA-Vegf-A or control shRNA was administered to the adventitia of the outflow vein, and a second dose of the same treatment was administered 14 days later. Animals were sacrificed at 21 days, 28 days, and 42 days after AVF creation for reverse transcription polymerase chain reaction and histomorphometric analyses. Results: By day 21, there was a 125{\%} increase in the average LVA (day 21, P = .11), with a decrease in cell proliferation (day 21, P = .0079; day 28, P = .28; day 42, P = .5), decrease in α-smooth muscle cell actin staining (day 21, P <.0001; day 28, P <.05; day 42, P = .59), and decrease in hypoxic stress (day 21, P <.001; day 28, P = .28; day 42, P = .46) in LV versus control shRNA vessels. Conclusions: A second dose of LV-shRNA-Vegf-A administration results in a moderate improvement in LVA at day 21.",
author = "Rajiv Janardhanan and Binxia Yang and Sreenivasulu Kilari and Leof, {Edward B} and Debabrata Mukhopadhyay and Sanjay Misra",
year = "2015",
month = "6",
day = "30",
doi = "10.1016/j.jvir.2015.12.751",
language = "English (US)",
journal = "Journal of Vascular and Interventional Radiology",
issn = "1051-0443",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation

AU - Janardhanan, Rajiv

AU - Yang, Binxia

AU - Kilari, Sreenivasulu

AU - Leof, Edward B

AU - Mukhopadhyay, Debabrata

AU - Misra, Sanjay

PY - 2015/6/30

Y1 - 2015/6/30

N2 - Purpose: To determine if a second dose of a lentivirus mediated small hairpin RNA that inhibits Vegf-A gene expression (LV-shRNA-Vegf-A) can improve lumen vessel area (LVA) of the outflow vein of an arteriovenous fistula (AVF) and decrease venous neointimal hyperplasia. Materials and Methods: Chronic kidney disease was created in C57BL/6 mice; 28 days later, an AVF was created by connecting the right carotid artery to the ipsilateral jugular vein. Immediately after AVF creation, 5 × 106 plaque-forming units of LV-shRNA-Vegf-A or control shRNA was administered to the adventitia of the outflow vein, and a second dose of the same treatment was administered 14 days later. Animals were sacrificed at 21 days, 28 days, and 42 days after AVF creation for reverse transcription polymerase chain reaction and histomorphometric analyses. Results: By day 21, there was a 125% increase in the average LVA (day 21, P = .11), with a decrease in cell proliferation (day 21, P = .0079; day 28, P = .28; day 42, P = .5), decrease in α-smooth muscle cell actin staining (day 21, P <.0001; day 28, P <.05; day 42, P = .59), and decrease in hypoxic stress (day 21, P <.001; day 28, P = .28; day 42, P = .46) in LV versus control shRNA vessels. Conclusions: A second dose of LV-shRNA-Vegf-A administration results in a moderate improvement in LVA at day 21.

AB - Purpose: To determine if a second dose of a lentivirus mediated small hairpin RNA that inhibits Vegf-A gene expression (LV-shRNA-Vegf-A) can improve lumen vessel area (LVA) of the outflow vein of an arteriovenous fistula (AVF) and decrease venous neointimal hyperplasia. Materials and Methods: Chronic kidney disease was created in C57BL/6 mice; 28 days later, an AVF was created by connecting the right carotid artery to the ipsilateral jugular vein. Immediately after AVF creation, 5 × 106 plaque-forming units of LV-shRNA-Vegf-A or control shRNA was administered to the adventitia of the outflow vein, and a second dose of the same treatment was administered 14 days later. Animals were sacrificed at 21 days, 28 days, and 42 days after AVF creation for reverse transcription polymerase chain reaction and histomorphometric analyses. Results: By day 21, there was a 125% increase in the average LVA (day 21, P = .11), with a decrease in cell proliferation (day 21, P = .0079; day 28, P = .28; day 42, P = .5), decrease in α-smooth muscle cell actin staining (day 21, P <.0001; day 28, P <.05; day 42, P = .59), and decrease in hypoxic stress (day 21, P <.001; day 28, P = .28; day 42, P = .46) in LV versus control shRNA vessels. Conclusions: A second dose of LV-shRNA-Vegf-A administration results in a moderate improvement in LVA at day 21.

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SN - 1051-0443

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