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A Method for Labeling Vasculature in Embryonic Mice
Published on: October 7, 2011
Lactadherin promotes VEGF-dependent neovascularization
Jean-Sébastien Silvestre1, Clotilde Théry, Ghislaine Hamard
1Cardiovascular Research Center INSERM U689 Lariboisière, Université Paris 7, Hôpital Lariboisière, 41 bvd de la chapelle, 75475 Paris cedex 10, France.
Nature Medicine
|April 19, 2005
Summary
Lactadherin, a milk protein, is crucial for blood vessel growth (neovascularization) by interacting with integrins and influencing vascular endothelial growth factor (VEGF) signaling. This discovery highlights lactadherin as a potential target for therapies aimed at modulating blood vessel formation.
Area of Science:
- * Molecular and Cellular Biology
- * Angiogenesis Research
- * Integrin Signaling
Background:
- * Vascular endothelial growth factor (VEGF)-induced angiogenesis is critical for physiological and pathological processes.
- * Integrin-mediated signaling is essential for VEGF-driven blood vessel growth.
- * The role of milk fat globule-EGF factor 8 (MFG-E8), also known as lactadherin, in vascular biology was previously unexplored.
Purpose of the Study:
- * To investigate the role of lactadherin in VEGF-dependent neovascularization in adult mice.
- * To determine the interaction of lactadherin with specific integrins (alphavbeta3 and alphavbeta5).
- * To assess the impact of lactadherin on VEGF-mediated signaling pathways, specifically Akt phosphorylation.
Main Methods:
- * Utilized neutralizing antibodies against lactadherin.
- * Employed lactadherin-deficient mouse models.
- * Performed in vitro studies on endothelial cells and in vivo assessments of post-ischemic neovascularization.
Main Results:
- * Lactadherin is expressed in and around blood vessels and plays a key role in VEGF-dependent neovascularization.
- * Lactadherin interacts with alphavbeta3 and alphavbeta5 integrins, modulating VEGF-dependent Akt phosphorylation and neovascularization.
- * Administration of lactadherin enhanced Akt phosphorylation and significantly improved post-ischemic neovascularization, even without VEGF stimulation.
Conclusions:
- * Lactadherin is a critical mediator of VEGF-dependent neovascularization in adult mice.
- * Lactadherin's interaction with alphavbeta3 and alphavbeta5 integrins is vital for its pro-angiogenic effects.
- * Lactadherin represents a significant therapeutic target for controlling neovascularization in various conditions.
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