title: PKCε is a negative regulator of PVAT-derived vessel formation.
abstract: BACKGROUND
  Vessel formation is a crucial event in tissue repair after injury. Thus, one assumption of innovative therapeutic approaches is the understanding of its molecular mechanisms. Notwithstanding our knowledge of the role of Protein Kinase C epsilon (PKCε) in cardio-protection and vascular restenosis, its role in vessel progenitor differentiation remains elusive.
  
  
  OBJECTIVE
  Given the availability of PKCε pharmacological modulators already tested in clinical trials, the specific aim of this study is to unravel the role of PKCε in vessel progenitor differentiation, with implications in vascular pathology and vasculogenesis.
  
  
  RESULTS
  Mouse Peri-Vascular Adipose Tissue (PVAT) was used as source of mesenchymal vessel progenitors. VEGF-induced differentiation of PVAT cells down-regulates both PKCε and p-PAK1 protein expression levels. PKCε overexpression and activation: i) reduced the expression levels of SMA and PECAM in endothelial differentiation of PVAT cells; ii) completely abrogated tubules formation in collagen gel assays; iii) increased the expression of p-PAK1.
  
  
  CONCLUSIONS
  PKCε negatively interferes with vessel progenitor differentiation via interaction with PAK-1.
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), Anatomy & Histology Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Galli
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), Anatomy & Histology Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Carubbi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Masselli
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), Anatomy & Histology Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Corradi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Dei Cas
authors.affiliation: Department of Clinical Sciences Sec. Internal Medicine and Critical Long-Term Care University Hospital, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Nouvenne
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), Anatomy & Histology Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bucci
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), Anatomy & Histology Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Arcari
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), Anatomy & Histology Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Mirandola
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), Anatomy & Histology Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy. Electronic address: marco.vitale@unipr.it.
authors.forename: M
authors.initials: M
authors.lastname: Vitale
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), Anatomy & Histology Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Gobbi
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000273:Adipose Tissue / Q000166:cytology*; D063194:Adventitia / Q000166:cytology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D002454:Cell Differentiation; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000201:enzymology; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology*; D004789:Enzyme Activation; D051379:Mice; D008840:Microfilament Proteins / Q000096:biosynthesis; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D051744:Protein Kinase C-epsilon / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D051785:Smad Proteins / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D054462:p21-Activated Kinases / Q000096:biosynthesis*; D000096985:Calponins
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051744:Protein Kinase C-epsilon; D051785:Smad Proteins; D042461:Vascular Endothelial Growth Factor A; D054462:p21-Activated Kinases; D000096985:Calponins; C467480:vascular endothelial growth factor A, mouse; C515905:Pak1 protein, mouse
keywords: Differentiation; PKCε; Peri-Vascular Adipose Tissue; Vascular progenitor