Conditional switching of VEGF provides new insights into adult neovascularization and pro-angiogenic therapy.

Dor, Yuval; Djonov, Valentin; Abramovitch, Rinat; Itin, Ahuva; Fishman, Glenn I; Carmeliet, Peter; Goelman, Gadi; Keshet, Eli (2002). Conditional switching of VEGF provides new insights into adult neovascularization and pro-angiogenic therapy. The EMBO journal, 21(8), pp. 1939-1947. EMBO Press 10.1093/emboj/21.8.1939

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To gain insight into neovascularization of adult organs and to uncover inherent obstacles in vascular endothelial growth factor (VEGF)-based therapeutic angiogenesis, a transgenic system for conditional switching of VEGF expression was devised. The system allows for a reversible induction of VEGF specifically in the heart muscle or liver at any selected schedule, thereby circumventing embryonic lethality due to developmental misexpression of VEGF. Using this system, we demonstrate a progressive, unlimited ramification of the existing vasculature. In the absence of spatial cues, however, abnormal vascular trees were produced, a consequence of chaotic connections with the existing network and formation of irregularly shaped sac-like vessels. VEGF also caused a massive and highly disruptive edema. Importantly, premature cessation of the VEGF stimulus led to regression of most acquired vessels, thus challenging the utility of therapeutic approaches relying on short stimulus duration. A critical transition point was defined beyond which remodeled new vessels persisted for months after withdrawing VEGF, conferring a long-term improvement in organ perfusion. This novel genetic system thus highlights remaining problems in the implementation of pro-angiogenic therapy.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy

UniBE Contributor:

Djonov, Valentin Georgiev

ISSN:

0261-4189

Publisher:

EMBO Press

Language:

English

Submitter:

David Christian Haberthür

Date Deposited:

04 Feb 2021 14:54

Last Modified:

04 Feb 2021 15:03

Publisher DOI:

10.1093/emboj/21.8.1939

PubMed ID:

11953313

BORIS DOI:

10.48350/149304

URI:

https://boris.unibe.ch/id/eprint/149304

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