PPARα 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. METHODOLOGY/PRINCIPAL FINDINGS: We studied the effects of MPs obtained from wild type (MPs(PPARα+/+)) and knock-out (MPs(PPARα−/−)) 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(PPARα+/+) or MPs(PPARα−/−) obtained from blood of mice. Only MPs(PPARα+/+) harboring PPAR(α) significantly increased EPC, but not monocytic, differentiation. Bone marrow-derived cells treated with MPs(PPARα+/+) displayed increased expression of pro-angiogenic genes and increased in vivo angiogenesis. MPs(PPARα+/+) increased capillary-like tube formation of endothelial cells that was associated with enhanced expressions of endothelial cell-specific markers. Finally, the effects of MPs(PPARα+/+) were mediated by NF-κB-dependent mechanisms. CONCLUSIONS/SIGNIFICANCE: Our 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.