pro-angiogenic effect of rantes-loaded polysaccharide-based microparticles for a mouse ischemia therapy

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ID: 139637
2017
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Abstract
Abstract Peripheral arterial disease results from the chronic obstruction of arteries leading to critical hindlimb ischemia. The aim was to develop a new therapeutic strategy of revascularization by using biodegradable and biocompatible polysaccharides-based microparticles (MP) to treat the mouse hindlimb ischemia. For this purpose, we deliver the pro-angiogenic chemokine Regulated upon Activation, Normal T-cell Expressed and Secreted (RANTES)/CCL5 in the mouse ischemic hindlimb, in solution or incorporated into polysaccharide-based microparticles. We demonstrate that RANTES-loaded microparticles improve the clinical score, induce the revascularization and the muscle regeneration in injured mice limb. To decipher the mechanisms underlying RANTES effects in vivo, we demonstrate that RANTES increases the spreading, the migration of human endothelial progenitor cells (EPC) and the formation of vascular network. The main receptors of RANTES i.e. CCR5, syndecan-4 and CD44 expressed at endothelial progenitor cell surface are involved in RANTES-induced in vitro biological effects on EPC. By using two RANTES mutants, [E66A]-RANTES with impaired ability to oligomerize, and [44AANA47]-RANTES mutated in the main RANTES-glycosaminoglycan binding site, we demonstrate that both chemokine oligomerization and binding site to glycosaminoglycans are essential for RANTES-induced angiogenesis in vitro. Herein we improved the muscle regeneration and revascularization after RANTES-loaded MP local injection in mice hindlimb ischemia.
Reference Key
suffee2017scientificpro-angiogenic Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;N. Suffee;C. Le Visage;H. Hlawaty;R. Aid-Launais;V. Vanneaux;J. Larghero;O. Haddad;O. Oudar;N. Charnaux;A. Sutton
Journal historia de la educación
Year 2017
DOI
10.1038/s41598-017-13444-7
URL
http://link.springer.com/article/10.1038/s41598-017-13444-7
Keywords
medicinescience

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