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

Yuxi Feng; Franziska vom Hagen; Frederick Pfister; Snezana Djokic; Sigrid Hoffmann; Walter Back; Patrick Wagner; Jihong Lin; Urban Deutsch; Hans-Peter Hammes

doi:10.1160/TH06-05-0277

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

¹5^th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany

,

Franziska vom Hagen

¹5^th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany

,

Frederick Pfister

¹5^th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany

,

Snezana Djokic

¹5^th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany

,

Sigrid Hoffmann

²Medical Research Center, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany

,

Walter Back

³Institute of Pathology, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany

,

Patrick Wagner

⁴Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany

,

Jihong Lin

¹5^th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany

,

Urban Deutsch

⁴Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany

⁵Max-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

¹5^th Medical Clinic, Faculty of Clinical Medicine, University of Heidelberg, Mannheim, Germany

› Institutsangaben

Abstract

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

Volltext

Referenzen

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