Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells

Abstract : Objective Acidosis is present in several pathological conditions where vasculogenesis takes place including ischemia, tumor growth and wound healing. We have previously demonstrated that acidosis induces human CD34? cell apoptosis. Considering that endothelial colony forming cells (ECFC) are a subpopulation of CD34? cells and key players in vasculogenesis, in the present study we investigated the effect of acidosis on the survival and functionality of ECFC. Approach and Results Endothelial colony-forming cells obtained by differentiation of human cord blood CD34? cells in endothelial growth medium-2 for 14-21 days were exposed at pH 7.4, 7.0 or 6.6. We found that acidosis failed to induce ECFC apoptosis and, although an early reduction in proliferation, chemotaxis, wound healing and capillary-like tubule formation was observed, once the medium pH was restored to 7.4, ECFC proliferation and tubulogenesis were augmented. Stromal cell derived factor-1 (SDF1)-driven migration and chemokine receptor type 4 surface expression were also increased. The maximal proangio-genic effect exerted by acidic preconditioning was observed after 6 h at pH 6.6. Furthermore, preconditioned ECFC showed an increased ability to promote tissue revascularization in a murine model of hind limb ischemia. Immunoblotting assays showed that acidosis activated AKT and ERK1/2 and inhibited p38 pathways. Proliferation rises triggered by acidic preconditioning were no longer observed after AKT or ERK1/2 inhibition, whereas p38 suppression not only mimicked but also potentiated the effect of acidosis on ECFC tubule formation abilities. Conclusions These results demonstrate that acidic pre-conditioning greatly increases ECFC-mediated angiogene-sis in vitro including ECFC proliferation, tubulogenesis and SDF1-driven chemotaxis and is a positive regulator of microvessel formation in vivo.
Document type :
Journal articles
Complete list of metadatas

Cited literature [48 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01974025
Contributor : Catherine Boisson Vidal <>
Submitted on : Tuesday, January 8, 2019 - 3:22:39 PM
Last modification on : Thursday, April 11, 2019 - 4:02:25 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Hebe Mena, Anna Lokajczyk, Blandine Dizier, Sergio Strier, Liliana Voto, et al.. Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells. Angiogenesis, Springer Verlag, 2014, 17 (4), pp.867-879. ⟨10.1007/s10456-014-9434-5⟩. ⟨inserm-01974025⟩

Share

Metrics

Record views

115