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01.07.2014 | Original Paper

Targeting VEGFR1 on endothelial progenitors modulates their differentiation potential

verfasst von: Clément d’Audigier, Benoit Gautier, Alexis Yon, Jean-Meidi Alili, Coralie L. Guérin, Solène M. Evrard, Anne Godier, Skerdi Haviari, Marie Reille-Serroussi, Florent Huguenot, Blandine Dizier, Nicolas Inguimbert, Delphine Borgel, Ivan Bièche, Catherine Boisson-Vidal, Carmen Roncal, Peter Carmeliet, Michel Vidal, Pascale Gaussem, David M. Smadja

Erschienen in: Angiogenesis | Ausgabe 3/2014

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Abstract

Objectives

We studied whether plasma levels of angiogenic factors VEGF and placental growth factor (PlGF) in coronary artery disease patients or undergoing cardiac surgery are modified, and whether those factors modulate endothelial progenitor’s angiogenic potential.

Methods and results

A total of 143 patients’ plasmas from two different studies were analyzed (30 coronary artery disease patients, 30 patients with stable angina, coupled with 30 age and sex-matched controls; 53 patients underwent cardiac surgery). Among factors screened, only PlGF was found significantly increased in these pathological populations. PlGF-1 and PlGF-2 were then tested on human endothelial-colony-forming cells (ECFCs). We found that PlGF-1 and PlGF-2 induce VEGFR1 phosphorylation and potentiate ECFCs tubulogenesis in vitro. ECFCs VEGFR1 was further inhibited using a specific small interfering RNA (siRNA) and the chemical compound 4321. We then observed that the VEGFR1-siRNA and the compound 4321 decrease ECFCs tubulogenesis potential in vitro. Finally, we tested the compound 4321 in the preclinical Matrigel^®-plug model with C57Bl/6J mice as well as in the murine hindlimb ischemia model. We found that 4321 inhibited the plug vascularization, attested by the hemoglobin content and the VE-Cadherin expression level and that 4321 inhibited the post-ischemic revascularization.

Conclusion

PlGF plasma levels were found increased in cardiovascular patients. Disrupting PlGF/VEGFR1 pathway could modulate ECFC-induced tubulogenesis, the cell type responsible for newly formed vessels in vivo.

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Titel: Targeting VEGFR1 on endothelial progenitors modulates their differentiation potential
verfasst von: Clément d’Audigier
Benoit Gautier
Alexis Yon
Jean-Meidi Alili
Coralie L. Guérin
Solène M. Evrard
Anne Godier
Skerdi Haviari
Marie Reille-Serroussi
Florent Huguenot
Blandine Dizier
Nicolas Inguimbert
Delphine Borgel
Ivan Bièche
Catherine Boisson-Vidal
Carmen Roncal
Peter Carmeliet
Michel Vidal
Pascale Gaussem
David M. Smadja
Publikationsdatum: 01.07.2014
Verlag: Springer Netherlands
Erschienen in: Angiogenesis / Ausgabe 3/2014
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-013-9413-2

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Targeting VEGFR1 on endothelial progenitors modulates their differentiation potential

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Methods and results

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