title: Effects of Pleiotrophin on endothelial and inflammatory cells: Pro-angiogenic and anti-inflammatory properties and potential role for vascular bio-prosthesis endothelialization.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  EA.hy926 endothelial cells, THP-1 monocytes and PMA-differentiated macrophages were treated with Pleiotrophin (10 and 100ng/ml). VEGF, Flk-1, Nrp-1, COX-2, ICAM-1 and TGFβ expression were detected by Western Blot, IL-10, MCP-1 and TNFα 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 TNFα. In PMA-differentiated macrophages COX-2 expression was significantly reduced by Pleiotrophin, while IL-10 and TGFβ 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.
authors.affiliation: Vascular and Endovascular Surgery Unit, Research Laboratory of Experimental and Clinical, Vascular Biology, DISC, University of Genoa, IRCCS San Martino-IST, 16132 Genoa, Italy; Research Center of Biologically Inspired Engineering for Vascular Medicine and Longevity (BELONG), Genoa, Italy. Electronic address: danielapalmieri@yahoo.com.
authors.forename: Daniela
authors.initials: D
authors.lastname: Palmieri
authors.affiliation: Vascular and Endovascular Surgery Unit, Research Laboratory of Experimental and Clinical, Vascular Biology, DISC, University of Genoa, IRCCS San Martino-IST, 16132 Genoa, Italy; Research Center of Biologically Inspired Engineering for Vascular Medicine and Longevity (BELONG), Genoa, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Mura
authors.affiliation: Vascular and Endovascular Surgery Unit, Research Laboratory of Experimental and Clinical, Vascular Biology, DISC, University of Genoa, IRCCS San Martino-IST, 16132 Genoa, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Mambrini
authors.affiliation: Vascular and Endovascular Surgery Unit, Research Laboratory of Experimental and Clinical, Vascular Biology, DISC, University of Genoa, IRCCS San Martino-IST, 16132 Genoa, Italy; Research Center of Biologically Inspired Engineering for Vascular Medicine and Longevity (BELONG), Genoa, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palombo
mesh_terms: D002352:Carrier Proteins / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; C066845:pleiotrophin
keywords: Endothelial cells; Endothelialization; Inflammatory cells; Pleiotrophin; Vascular graft