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Archives of cardiovascular diseases
Volume 102, n° S1
pages 40-41 (mars 2009)
Doi : 10.1016/S1875-2136(09)72223-5
D013 PPAR-alpha is essential for microparticleinduced differentiation of bone marrow-derived endothelial progenitor cells and in vitro angiogenesis

T. Benameur, S. Tual-Chalot, R. Andriantsitohaina, M.-C. Martinez
UMR-CNRS 6214 Inserm 771, Angers, France 


Bone marrow-derived endothelial progenitor cells (EPCs), present in the systemic circulation, are augmented in response to tissue ischemia, and incorporate into sites of neovascularization. They possess the ability to differentiate into endothelial cells (ECs). Microparticles (MPs), small fragments generated from the plasma membrane, are able to activate the angiogenic program of ECs through mRNA transfer. Also, Peroxisome Proliferator-Activated Receptor (PPAR) alpha agonists increase cardiac progenitor differentiation. Here, we have studied the effects of circulating MPs obtained from PPARalpha wild type (WT) and knock-out (KO) mice on EPC differentiation and in vitro capillary-like tube formation of ECs.

MPs were obtained from blood of mice, and MP sub-populations were characterized by flow cytometer. EPCs were isolated from WT mice using density gradient separation. Isolated cells were cultured in the absence or presence of MPs from PPARalpha WT or KO mice for 7 days. Then, expression of specific markers of EPCs (Sca-1/Flk-1) were analysed by flow cytometry or dual binding of FITC-labeled BS I lectin and Dil-acetylated-LDL by confocal microscopy. Also, ECs were isolated from WT mice aorta. The effects of 24 hours incubation with MPs from PPARalpha WT or KO mice on in vitro angiogenesis were assessed by capillary-like tube formation assay on Matrigel.

Circulating MPs from PPARalpha mice were mainly derived from platelets and leucocytes. MP levels were not significantly different between strains. Only MPs from PPARalpha WT mice harbored PPARalpha. Incubation of EPCs with MPs from PPARalpha WT, but not from KO mice, increased significantly the number of differentiated EPCs. Incubation of ECs with PPARalpha WT-derived MPs increased capillary-like tube formation of ECs. By contrast, deletion of PPARalpha markedly inhibited in vitro tube formation of ECs.

Our results suggest that the presence of PPARalpha in MPs, not only stimulates EPCs differentiation, but also favored in vitro angiogenesis of ECs. These findings provide a new alternative approach for cell therapy of cardiovascular pathologies associated with impaired angiogenesis that might include injection of EPCs treated with PPARalpha MPs.

Supported by Fondation de France.

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