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Thromb Haemost 2007; 97(01): 99-108
DOI: 10.1160/TH06-05-0277
Endothelium and Vascular Development
Schattauer GmbH

Impaired pericyte recruitment and abnormal retinal angiogenesis as a result of angiopoietin-2 overexpression

Yuxi Feng
1   5th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany
,
Franziska vom Hagen
1   5th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany
,
Frederick Pfister
1   5th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany
,
Snezana Djokic
1   5th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany
,
Sigrid Hoffmann
2   Medical Research Center, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany
,
Walter Back
3   Institute of Pathology, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany
,
Patrick Wagner
4   Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany
,
Jihong Lin
1   5th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany
,
Urban Deutsch
4   Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany
5   Max-Planck-Institute for Vascular Biology, c/o Institute of Cell Biology, ZMBE, University of Muenster, Muenster, Germany and Theodor Kocher Institute, University of Berne, Berne, Switzerland
,
Hans-Peter Hammes
1   5th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany
› Author Affiliations
Further Information

Publication History

Received 18 May 2006

Accepted after resubmission 05 November 2006

Publication Date:
28 November 2017 (online)

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Summary

Angiopoietin-2 (Ang2) is among the relevant growth factors induced by hypoxia and plays an important role in the initiation of retinal neovascularizations. Ang2 is also involved in incipient diabetic retinopathy, as it may cause pericyte loss. To investigate the impact of Ang2 on developmental and hypoxia-induced angiogenesis, we used a transgenic mouse line overexpressing human Ang2 in the mouse retina. Transgenic mice displayed a reduced coverage of capillaries with pericytes (-14 %; p<0.01) and a 46% increase of vascular density of the capillary network at postnatal day 10 compared to wild type mice. In the model of oxygen-induced retinopathy (OIR), Ang2 overexpression resulted in enhanced preretinal (+103%) and intraretinal neovascularization (+29%). Newly formed intraretinal vessels in OIR were also pericyte-deficient (-26 %; p<0.01). The total expression of Ang2 in transgenic mice was seven-fold, compared with wild type controls. Ang2 modulated expression of genes encoding VEGF (+65%) and Ang1 (+79%) in transgenic animals. These data suggest that Ang2 is involved in pericyte recruitment, and modulates intraretinal, and preretinal vessel formation in the eye under physiological and pathological conditions.

Keywords

Angiopoietin-2 - pericyte - angiogenesis - hypoxia - neovascularization
 

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