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B2-kinin receptor plays a key role in B1-, angiotensin converting enzyme inhibitor-, and vascular endothelial growth factor-stimulated in vitro angiogenesis in the hypoxic mouse heart

Sanchez de Miguel, Lourdes and Neysari, Shiva and Jakob, Sonja and Petrimpol, Marco and Butz, Nicole and Banfi, Andrea and Zaugg, Christian E. and Humar, Rok and Battegay, Edouard J.. (2008) B2-kinin receptor plays a key role in B1-, angiotensin converting enzyme inhibitor-, and vascular endothelial growth factor-stimulated in vitro angiogenesis in the hypoxic mouse heart. Cardiovascular research, Vol. 80, H. 1. pp. 106-113.

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Official URL: http://edoc.unibas.ch/dok/A5839827

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Abstract

AIMS: Angiotensin converting enzyme (ACE) inhibition reduces heart disease and vascular stiffness in hypertension and leads to kinin accumulation. In this study, we analysed the role and importance of two kinin receptor subtypes in angiogenesis during ACE inhibition in an in vitro model of angiogenesis of the mouse heart. METHODS AND RESULTS: First, we analysed the angiogenic properties of bradykinin and enalapril on wild-type C57Bl/6 and B2 receptor(-/-) mouse heart under normoxia (21% O(2)) and hypoxia (1% O(2)) in vitro and the contribution of B1 and B2 kinin receptors to this effect. Bradykinin induced dose-dependent endothelial sprout formation in vitro in adult mouse heart only under hypoxia (1.7 fold, n = 6, P > 0.05). The B2 receptor mediated sprouting that was induced by bradykinin and vascular endothelial growth factor (VEGF(164); n = 6, P > 0.05), but did not mediate sprouting that was induced by growth factors bFGF or PDGF-BB. Enalapril induced sprouting through both the B1 and B2 kinin receptors, but it required the presence of the B2 receptor in both scenarios and was dependent on BK synthesis. B1-receptor agonists induced sprout formation via the B1 receptor (2.5 fold, n = 6, P > 0.05), but it required the presence of the B2 receptor for them to do so. Both B2-receptor and B1-receptor agonist-induced angiogenesis required nitric oxide biosynthesis. CONCLUSION: The kinin B2 receptor plays a crucial role in angiogenesis that is induced by different vasoactive molecules, namely bradykinin, ACE inhibitors, B1-stimulating kinin metabolites, and VEGF164 in an in vitro model of angiogenesis of mouse heart under hypoxia. Therapeutic treatment of hypertensive patients by using ACE inhibitors may potentially benefit the ischaemic heart through inducing B2-dependent heart neovascularization.
Faculties and Departments:03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung > Chirurgische Forschung (Heberer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung > Chirurgische Forschung (Heberer)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Kardiologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Kardiologie
UniBasel Contributors:Zaugg, Christian E. and Banfi, Andrea
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Oxford University Press
ISSN:0008-6363
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:22
Deposited On:08 Nov 2012 16:13

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