PPARα Is Essential for Microparticle-Induced Differentiation of Mouse Bone Marrow-Derived Endothelial Progenitor Cells and Angiogenesis

BackgroundBone 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.
Methodology/Principal FindingsWe studied the effects of MPs obtained from wild type (MPsPPARα+/+) and knock-out (MPsPPARα−/−) mice on EPC differentiation and angiogenesis. Bone marrow-derived cells were isolated from WT or KO mice and were cultured in the presence of MPsPPARα+/+ or MPsPPARα−/− obtained from blood of mice. Only MPsPPARα+/+ harboring PPARα significantly increased EPC, but not monocytic, differentiation. Bone marrow-derived cells treated with MPsPPARα+/+ displayed increased expression of pro-angiogenic genes and increased in vivo angiogenesis. MPsPPARα+/+ increased capillary-like tube formation of endothelial cells that was associated with enhanced expressions of endothelial cell-specific markers. Finally, the effects of MPsPPARα+/+ were mediated by NF-κB-dependent mechanisms.
Conclusions/SignificanceOur results underscore the obligatory role of PPARα carried by MPs for EPC differentiation and angiogenesis. PPARα-NF-κB-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.