Designed angiopoietin-1 variant, COMP-Ang1, protects against radiation-induced endothelial cell apoptosis.

Abstract:

:Radiation therapy is a widely used cancer treatment, but it causes side effects even when localized radiotherapy is used. Extensive apoptosis of microvascular endothelial cells of the lamina propria is the primary lesion initiating intestinal radiation damage after abdominal radiation therapy. Many in vitro studies suggest that angiopoietin-1 (Ang1) has potential therapeutic applications in enhancing endothelial cell survival. For in vivo use, we developed a soluble, stable, and potent Ang1 variant, COMP-Ang1. COMP-Ang1 is more potent than native Ang1 in phosphorylating the Tie2 receptor in lung endothelial cells in vivo. Interestingly, COMP-Ang1 administered i.v. was mainly localized to microvascular endothelial cells of the intestinal villi and lung but not to microvascular endothelial cells of the liver. In irradiated mice, i.v. COMP-Ang1 protected against radiation-induced apoptosis in microcapillary endothelial cells of the intestinal villi and prolonged survival. Thus, COMP-Ang1 could be used as a therapeutic protein for specific protection against endothelial cell injury.

authors

Cho CH,Kammerer RA,Lee HJ,Yasunaga K,Kim KT,Choi HH,Kim W,Kim SH,Park SK,Lee GM,Koh GY

doi

10.1073/pnas.0307575101

keywords:

subject

Has Abstract

pub_date

2004-04-13 00:00:00

pages

5553-8

issue

15

eissn

0027-8424

issn

1091-6490

pii

0307575101

journal_volume

101

pub_type

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