Effects of Pleiotrophin on endothelial and inflammatory cells: Pro-angiogenic and anti-inflammatory properties and potential role for vascular bio-prosthesis endothelialization

Purpose: One of the limitations emerged with both synthetic and degradable vascular grafts is the lack of endothelialization after implantation that is known to be the main reason leading to unfavourable outcomes. It emerges the need to find new strategies to promote a rapid endothelialization of the scaffold. Pleiotrophin is a growth/differentiation cytokine for various cell type. We here evaluated the effect of Pleiotrophin on endothelial cells (EC), monocytes and macrophages that have been shown as key cells promoting neovascularization. Material/methods: EA. hy926 endothelial cells, THP-1 monocytes and PMA-differentiated macrophages were treated with Pleiotrophin (10 and 100 ng/ml). VEGF, Flk-1, Nrp-1, COX-2, ICAM-1 and TGF beta expression were detected by Western Blot, IL-10, MCP-1 and TNF alpha levels by ELISA. Chemotaxis was performed in Boyden chambers. Wound healing was performed by scratch wound assay. Results: Pleiotrophin induces in EC the expression of VEGF and its receptors Flk-1 and Nrp-1 and improves the migratory capacity. In THP-1 monocytes, Pleiotrophin induces the expression of VEGF and its receptor Nrp-1 and decreases the levels of COX-2 and TNFa. In PMA-differentiated macrophages COX-2 expression was significantly reduced by Pleiotrophin, while IL-10 and TGFb were increased. Conclusions: Pleiotrophin acts as an angiogenesis 'driver' by promoting the creation of a pro-angiogenic environment, a migratory behaviour in EC and a pro-regenerative alternative phenotype in macrophages. Our results suggest that Pleiotrophin might be considered for vascular prosthesis engineering. (C) 2015 Medical University of Bialystok. Published by Elsevier Sp. z o. o. All rights reserved.