Published online before print July 27, 2006, doi: 10.1161/01.ATV.0000238356.20565.92
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© 2006 American Heart Association, Inc.
Vascular Biology |
Atypical GPI-Anchored T-Cadherin Stimulates Angiogenesis In Vitro and In Vivo
From the Cardiovascular Signalling Group (M.P., D.I., R.A., T.R.), Department of Research, and Cell and Gene Therapy Group (A.B.), Departments of Surgery and of Research, Basel University Hospital, and Division of Cardiology (P.E.), Kantonsspital Luzern, Switzerland.
Correspondence to Dr Maria Philippova, Cardiovascular Signalling, ZLF 316, Basel University Hospital, Hebelstrasse 20, CH-4031 Basel, Switzerland. E-mail maria.filippova{at}unibas.ch
Objective— T-cadherin (T-cad) is an atypical GPI-anchored member of the cadherin superfamily. In vascular tissue, T-cad expression is increased during atherosclerosis, restenosis, and tumor neovascularization. In vitro, overexpression and/or homophilic ligation of T-cad on endothelial cells (ECs) facilitates migration, proliferation, and survival. This study investigated T-cad effects on angiogenesis.
Methods and Results— In vitro, T-cad homophilic ligation induced arrangement of ECs into a capillary-like network in a 2-dimensional model of EC differentiation and stimulated in-gel endothelial sprout outgrowth in an EC spheroid model and a modified Nicosia tissue assay. Sprouting from spheroids composed of adenoviral-infected T-cad overexpressing ECs or T-cad siRNA transfected ECs were significantly increased or reduced, respectively. In vivo, T-cad potentiated VEGF effects on neovascularization in a model of myoblast-mediated gene transfer to mouse skeletal muscle; vessel caliber after co-delivery of T-cad and VEGF was significantly greater than after delivery of VEGF alone.
Conclusions— We unequivocally identify T-cad as a novel modulator of angiogenesis and suggest that this molecule can be exploited as a target for modulation of therapeutic angiogenesis, as well as for prevention of pathological conditions associated with abnormal neovascularization.
This study demonstrates that GPI-anchored T-cadherin stimulates angiogenesis in 2-dimensional model of endothelial differentiation, in 3-dimensional endothelial spheroid, and Nicosia tissue assays in vitro. In vivo, T-cad potentiates VEGF effects on neovascularization in mouse skeletal muscle. We conclude that T-cad is a novel modulator of angiogenesis.
Key Words: angiogenesis • cadherin • endothelial cell differentiation • VEGF
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