A Potent Anti-angiogenic Factor, Vasohibin-1, Ameliorates Experimental Bronchiolitis Obliterans

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• 作者：T. Watanabe^a ; ^b ; Y. Okada^a ; ^{yokada@idac.tohoku.ac.jp} ; Y. Hoshikawa^a ; S. Eba^a ; H. Notsuda^a ; Y. Watanabe^b ; H. Ohishi^a ; Y. Sato^b ; T. Kondo^a
• 刊名：Transplantation Proceedings
• 出版年：2012
• 期刊代码：252_00411345
• 类别：med
• 出版时间：May, 2012
• 卷：44
• 期：4
• 页码：1155-1157
• 文件大小：298 K

摘要

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.