A potent anti-angiogenic factor, vasohibin-1, ameliorates experimental bronchiolitis obliterans

T. Watanabe, Y. Okada, Yasushi Hoshikawa, S. Eba, H. Notsuda, Y. Watanabe, H. Ohishi, Y. Sato, T. Kondo

Research output: Contribution to journalArticle

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Abstract

Background: Bronchiolitis obliterans (BO) is a major cause of morbidity and mortality after lung transplantation. BO is pathologically characterized by neovascularized fibro-obliteration of the allograft airway. A recent study has shown that aberrant angiogenesis during fibro-obliteration contributes to the pathogenesis of BO. Vasohibin-1 (VASH1) has been isolated as a vascular endothelial growth factor-inducible gene in endothelial cells (ECs) that inhibits migration and proliferation of ECs and exhibits anti-angiogenic activity in vivo. Purpose: This study examines whether VASH1 inhibits fibro-obliteration of the allograft in a murine intrapulmonary tracheal transplantation model. Method: Tracheal allografts of BALB/c mouse were transplanted into the left lung of recipient C57BL/6J mouse. We performed gene transfer to the recipient lungs using an adenovirus vector encoding human VASH1 (Ad-VASH1) or beta- garactosidase (Ad-LacZ) as the control. Tracheal allografts were harvested and pathological on days 21 and 28. Result: Ad-VASH1 treatment reduced the vascular area on day 21 (4.6% versus 13.0%, P =.037) and day 28 (5.4% versus 13.4%, P =.022) compared with the control group. This was accompanied by significantly inhibited luminal obliteration of the tracheal allografts in the animals transferred with Ad-VASH1 compared with the control (69% versus 93%, P =.028) on day 21. We were not able to observe this effect on day 28 (92% versus 97%, P =.48). Conclusion: Transgene expression of VASH1 in the recipient lung significantly attenuated luminal obliteration of the tracheal allograft; this was associated with significantly reduced aberrant angiogenesis in the fibro-obliterative tissue in a murine model intrapulmonary tracheal transplantation.

Original languageEnglish
Pages (from-to)1155-1157
Number of pages3
JournalTransplantation Proceedings
Volume44
Issue number4
DOIs
Publication statusPublished - 01-05-2012

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Bronchiolitis Obliterans
Angiogenesis Inducing Agents
Allografts
Lung
Endothelial Cells
Transplantation
Lung Transplantation
Transgenes
Inbred C57BL Mouse
Adenoviridae
Vascular Endothelial Growth Factor A
Genes
Cell Movement
Blood Vessels
Cell Proliferation
Morbidity
Control Groups
Mortality

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

Cite this

Watanabe, T. ; Okada, Y. ; Hoshikawa, Yasushi ; Eba, S. ; Notsuda, H. ; Watanabe, Y. ; Ohishi, H. ; Sato, Y. ; Kondo, T. / A potent anti-angiogenic factor, vasohibin-1, ameliorates experimental bronchiolitis obliterans. In: Transplantation Proceedings. 2012 ; Vol. 44, No. 4. pp. 1155-1157.
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title = "A potent anti-angiogenic factor, vasohibin-1, ameliorates experimental bronchiolitis obliterans",
abstract = "Background: Bronchiolitis obliterans (BO) is a major cause of morbidity and mortality after lung transplantation. BO is pathologically characterized by neovascularized fibro-obliteration of the allograft airway. A recent study has shown that aberrant angiogenesis during fibro-obliteration contributes to the pathogenesis of BO. Vasohibin-1 (VASH1) has been isolated as a vascular endothelial growth factor-inducible gene in endothelial cells (ECs) that inhibits migration and proliferation of ECs and exhibits anti-angiogenic activity in vivo. Purpose: This study examines whether VASH1 inhibits fibro-obliteration of the allograft in a murine intrapulmonary tracheal transplantation model. Method: Tracheal allografts of BALB/c mouse were transplanted into the left lung of recipient C57BL/6J mouse. We performed gene transfer to the recipient lungs using an adenovirus vector encoding human VASH1 (Ad-VASH1) or beta- garactosidase (Ad-LacZ) as the control. Tracheal allografts were harvested and pathological on days 21 and 28. Result: Ad-VASH1 treatment reduced the vascular area on day 21 (4.6{\%} versus 13.0{\%}, P =.037) and day 28 (5.4{\%} versus 13.4{\%}, P =.022) compared with the control group. This was accompanied by significantly inhibited luminal obliteration of the tracheal allografts in the animals transferred with Ad-VASH1 compared with the control (69{\%} versus 93{\%}, P =.028) on day 21. We were not able to observe this effect on day 28 (92{\%} versus 97{\%}, P =.48). Conclusion: Transgene expression of VASH1 in the recipient lung significantly attenuated luminal obliteration of the tracheal allograft; this was associated with significantly reduced aberrant angiogenesis in the fibro-obliterative tissue in a murine model intrapulmonary tracheal transplantation.",
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Watanabe, T, Okada, Y, Hoshikawa, Y, Eba, S, Notsuda, H, Watanabe, Y, Ohishi, H, Sato, Y & Kondo, T 2012, 'A potent anti-angiogenic factor, vasohibin-1, ameliorates experimental bronchiolitis obliterans', Transplantation Proceedings, vol. 44, no. 4, pp. 1155-1157. https://doi.org/10.1016/j.transproceed.2012.02.022

A potent anti-angiogenic factor, vasohibin-1, ameliorates experimental bronchiolitis obliterans. / Watanabe, T.; Okada, Y.; Hoshikawa, Yasushi; Eba, S.; Notsuda, H.; Watanabe, Y.; Ohishi, H.; Sato, Y.; Kondo, T.

In: Transplantation Proceedings, Vol. 44, No. 4, 01.05.2012, p. 1155-1157.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A potent anti-angiogenic factor, vasohibin-1, ameliorates experimental bronchiolitis obliterans

AU - Watanabe, T.

AU - Okada, Y.

AU - Hoshikawa, Yasushi

AU - Eba, S.

AU - Notsuda, H.

AU - Watanabe, Y.

AU - Ohishi, H.

AU - Sato, Y.

AU - Kondo, T.

PY - 2012/5/1

Y1 - 2012/5/1

N2 - Background: Bronchiolitis obliterans (BO) is a major cause of morbidity and mortality after lung transplantation. BO is pathologically characterized by neovascularized fibro-obliteration of the allograft airway. A recent study has shown that aberrant angiogenesis during fibro-obliteration contributes to the pathogenesis of BO. Vasohibin-1 (VASH1) has been isolated as a vascular endothelial growth factor-inducible gene in endothelial cells (ECs) that inhibits migration and proliferation of ECs and exhibits anti-angiogenic activity in vivo. Purpose: This study examines whether VASH1 inhibits fibro-obliteration of the allograft in a murine intrapulmonary tracheal transplantation model. Method: Tracheal allografts of BALB/c mouse were transplanted into the left lung of recipient C57BL/6J mouse. We performed gene transfer to the recipient lungs using an adenovirus vector encoding human VASH1 (Ad-VASH1) or beta- garactosidase (Ad-LacZ) as the control. Tracheal allografts were harvested and pathological on days 21 and 28. Result: Ad-VASH1 treatment reduced the vascular area on day 21 (4.6% versus 13.0%, P =.037) and day 28 (5.4% versus 13.4%, P =.022) compared with the control group. This was accompanied by significantly inhibited luminal obliteration of the tracheal allografts in the animals transferred with Ad-VASH1 compared with the control (69% versus 93%, P =.028) on day 21. We were not able to observe this effect on day 28 (92% versus 97%, P =.48). Conclusion: Transgene expression of VASH1 in the recipient lung significantly attenuated luminal obliteration of the tracheal allograft; this was associated with significantly reduced aberrant angiogenesis in the fibro-obliterative tissue in a murine model intrapulmonary tracheal transplantation.

AB - Background: Bronchiolitis obliterans (BO) is a major cause of morbidity and mortality after lung transplantation. BO is pathologically characterized by neovascularized fibro-obliteration of the allograft airway. A recent study has shown that aberrant angiogenesis during fibro-obliteration contributes to the pathogenesis of BO. Vasohibin-1 (VASH1) has been isolated as a vascular endothelial growth factor-inducible gene in endothelial cells (ECs) that inhibits migration and proliferation of ECs and exhibits anti-angiogenic activity in vivo. Purpose: This study examines whether VASH1 inhibits fibro-obliteration of the allograft in a murine intrapulmonary tracheal transplantation model. Method: Tracheal allografts of BALB/c mouse were transplanted into the left lung of recipient C57BL/6J mouse. We performed gene transfer to the recipient lungs using an adenovirus vector encoding human VASH1 (Ad-VASH1) or beta- garactosidase (Ad-LacZ) as the control. Tracheal allografts were harvested and pathological on days 21 and 28. Result: Ad-VASH1 treatment reduced the vascular area on day 21 (4.6% versus 13.0%, P =.037) and day 28 (5.4% versus 13.4%, P =.022) compared with the control group. This was accompanied by significantly inhibited luminal obliteration of the tracheal allografts in the animals transferred with Ad-VASH1 compared with the control (69% versus 93%, P =.028) on day 21. We were not able to observe this effect on day 28 (92% versus 97%, P =.48). Conclusion: Transgene expression of VASH1 in the recipient lung significantly attenuated luminal obliteration of the tracheal allograft; this was associated with significantly reduced aberrant angiogenesis in the fibro-obliterative tissue in a murine model intrapulmonary tracheal transplantation.

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