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

Cho, Chung Hyun; Kammerer, Richard A.; Lee, Hyuek Jong; Yasunaga, Kunio; Kim, Young Ho; Choi, Han Ho; Kim, Won; Kim, Sung Hyun; Park, Sung Kwang; Lee, Gyun Min; Koh, Gou Young

doi:10.1073/pnas.0307575101

Cited by 130 publications

(103 citation statements)

References 23 publications

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“…and sacrificed at the indicated times as previously described (Cho et al, 2004b). Lungs were harvested, cryo-sectioned, fixed with 1% paraformaldehyde for 5 min, embedded in paraffin, and immunostained with anti-Ang1 polyclonal Ab (PAhAng1FD-1).…”

Section: Immunohistochemical Localization Of Administered Comp-ang1mentioning

confidence: 99%

Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1

Lee

Lee²,

Kim³

et al. 2007

Exp Mol Med

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Inflammation of the asthmatic airway is usually accompanied by increased vascular permeability and plasma exudation. Angiopoietin-1 (Ang1) has potential therapeutic applications in preventing vascular leakage. Recently, we developed a soluble, stable, and potent Ang1 variant, COMP-Ang1. COMP-Ang1 is more potent than native Ang1 in phosphorylating the tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 receptor in lung endothelial cells. We have used a mouse model for allergic airway disease to determine effects of COMP-Ang1 on allergen-induced bronchial inflammation and airway hyper-responsiveness. These mice develop the following typical pathophysiological features of allergic airway disease in the lungs: increased numbers of inflammatory cells of the airways, airway hyper-responsiveness, increased levels of Th2 cell cytokines (IL-4, IL-5, and IL-13), adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), and chemokines (eotaxin and RANTES), and increased vascular permeability. Intravenous administration of COMP-Ang1 reduced bronchial inflammation and airway hyper-responsiveness. In addition, the increased plasma extravasation in allergic airway disease was significantly reduced by the administration of COMP-Ang1. These results suggest that COMP-Ang1 attenuates airway inflammation and hyper-responsiveness, prevents vascular leakage, and may be used as a therapeutic agent in allergic airway disease.

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Section: Immunohistochemical Localization Of Administered Comp-ang1mentioning

confidence: 99%

Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1

Lee

Lee²,

Kim³

et al. 2007

Exp Mol Med

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“…Furthermore, many in vitro studies suggest that angiopoietin-1 (Ang1) also has potential therapeutic applications in enhancing endothelial cell survival. For example, a potent Ang1 variant, COMP-Ang1 was studied in irradiated mice and was found to protect against radiation-induced apoptosis in microcapillary endothelial cells of the intestinal villi and leading to prolonged intestinal and systemic survival [46]. In the current study, angiopoietin is shown to be upregulated in both the small intestines and kidney.…”

Section: Discussionmentioning

confidence: 57%

Antagonists of growth hormone releasing hormone (GHRH) given before whole body radiation lead to modulation of radiation response and organ-specific changes in the expression of angiogenesis

et al. 2012

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Purpose This study seeks to determine if growth hormonereleasing hormone (GHRH) antagonist, JMR-132, increases survival when given before whole body radiation. Material and methods C3H mice were divided into 14 groups. The first 7 groups were given whole body radiation alone in the increasing doses of 7, 7.5, 8, 8.5, 9, 10, and 11 Gy, respectively. The other 7 groups received JMR-132 (10 μg/day s.c.) for 3 weeks then received the whole body radiation in increasing doses of 7, 7.5, 8, 8.5, 9, 10, and 11 Gy, respectively. The experiment lasted 35 days. Hazard ratios for survival were calculated for the addition of the GHRH antagonist as compared to radiation alone at the different dose levels. RT-PCR was performed to identify potential target genes. CD31 immunohistochemical staining identified the differences between average vessel count. Results Mice pretreated with JMR-132 showed a longer survival at lower radiation doses, the hazard ratios were 0.34 and 0.59 when the drug was given with doses of 7.5 and 8 Gy, respectively. A statistically significant higher hazard ratio of 3.48 and 4.22 was seen in mice when GHRH antagonist was added to doses of 10 and 11 Gy, respectively. Organ specific upregulation of several target genes such as Akt2, ATM, and Trp53 was seen with the GHRH antagonist. In the animals pretreated with JMR-132 the small intestine and the kidney showed higher average vessel count. Conclusion Pretreatment with GHRH antagonist JMR-132 protects at lower doses of radiation.

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“…L'origine de la lésion primaire -mort cellulaire des cellules souches de l'épithélium versus mort cellulaire des cellules endothéliales -est un sujet encore largement débattu. Depuis les travaux d 'Eddy et Casarett en 1968, un nombre varié d'approches a mis en avant le rôle important de l'apoptose radio-induite des cellules endothéliales dans l'atteinte de la muqueuse intestinale et finalement dans la survie de l'individu (Haimovitz-Friedman et al, 1997 ;Paris et al, 2001 ;Maj et al, 2003 ;Cho et al, 2004). Il a été montré que la protection des cellules endothéliales par un traitement avec un facteur de croissance, le basic fibroblast growth factor (bFGF), exerce un effet positif sur la survie, mais également sur la morphologie de l'intestin de souris irradiées.…”

Section: Conséquences Des Variations De La Circulation Sanguine Et Lyunclassified

Contribution des atteintes gastro-intestinales dans le développement du syndrome de défaillance multi-viscérale radio-induit

Monti¹,

Meeren²,

Griffiths³

2006

Radioprotection

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

Cited by 130 publications

References 23 publications

Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1

Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1

Antagonists of growth hormone releasing hormone (GHRH) given before whole body radiation lead to modulation of radiation response and organ-specific changes in the expression of angiogenesis

Contribution des atteintes gastro-intestinales dans le développement du syndrome de défaillance multi-viscérale radio-induit

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