PPARalpha is essential for microparticle-induced differentiation of mouse bone marrow-derived endothelial progenitor cells and angiogenesis.
BACKGROUND
Bone marrow-derived endothelial progenitor cells (EPCs) are critical for neovascularization. We hypothesized that microparticles (MPs), small fragments generated from the plasma membrane, can activate angiogenic programming of EPCs.


RESULTS
We studied the effects of MPs obtained from wild type (MPs(PPARalpha+/+)) and knock-out (MPs(PPARalpha-/-)) mice on EPC differentiation and angiogenesis. Bone marrow-derived cells were isolated from WT or KO mice and were cultured in the presence of MPs(PPARalpha+/+) or MPs(PPARalpha-/-) obtained from blood of mice. Only MPs(PPARalpha+/+) harboring PPAR(alpha) significantly increased EPC, but not monocytic, differentiation. Bone marrow-derived cells treated with MPs(PPARalpha+/+) displayed increased expression of pro-angiogenic genes and increased in vivo angiogenesis. MPs(PPARalpha+/+) increased capillary-like tube formation of endothelial cells that was associated with enhanced expressions of endothelial cell-specific markers. Finally, the effects of MPs(PPARalpha+/+) were mediated by NF-kappaB-dependent mechanisms.


CONCLUSIONS
Our results underscore the obligatory role of PPARalpha carried by MPs for EPC differentiation and angiogenesis. PPARalpha-NF-kappaB-Akt pathways may play a pivotal stimulatory role for neovascularization, which may, at least in part, be mediated by bone marrow-derived EPCs. Improvement of EPC differentiation may represent a useful strategy during reparative neovascularization.
Benameur
Tarek
T
CNRS, UMR 6214, Angers, France.
Tual-Chalot
Simon
S
Andriantsitohaina
Ramaroson
R
Martínez
María Carmen
MC
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002196:Capillaries / Q000378:metabolism; D002454:Cell Differentiation; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology*; D017353:Gene Deletion; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D018919:Neovascularization, Physiologic; D047493:PPAR alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D015854:Up-Regulation
D015415:Biomarkers; D016328:NF-kappa B; D047493:PPAR alpha; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt
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