title: Knockout of Density-Enhanced Phosphatase-1 impairs cerebrovascular reserve capacity in an arteriogenesis model in mice.
abstract: Collateral growth, arteriogenesis, represents a proliferative mechanism involving endothelial cells, smooth muscle cells, and monocytes/macrophages. Here we investigated the role of Density-Enhanced Phosphatase-1 (DEP-1) in arteriogenesis in vivo, a protein-tyrosine-phosphatase that has controversially been discussed with regard to vascular cell biology. Wild-type C57BL/6 mice subjected to permanent left common carotid artery occlusion (CCAO) developed a significant diameter increase in distinct arteries of the circle of Willis, especially in the anterior cerebral artery. Analyzing the impact of loss of DEP-1 function, induction of collateralization was quantified after CCAO and hindlimb femoral artery ligation comparing wild-type and DEP-1(-/-) mice. Both cerebral collateralization assessed by latex perfusion and peripheral vessel growth in the femoral artery determined by microsphere perfusion and micro-CT analysis were not altered in DEP-1(-/-) compared to wild-type mice. Cerebrovascular reserve capacity, however, was significantly impaired in DEP-1(-/-) mice. Cerebrovascular transcriptional analysis of proarteriogenic growth factors and receptors showed specifically reduced transcripts of PDGF-B. SiRNA knockdown of DEP-1 in endothelial cells in vitro also resulted in significant PDGF-B downregulation, providing further evidence for DEP-1 in PDGF-B gene regulation. In summary, our data support the notion of DEP-1 as positive functional regulator in vascular cerebral arteriogenesis, involving differential PDGF-B gene expression.
authors.affiliation: Center for Cardiovascular Research (CCR), Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité-University Medicine Berlin, Hessische Straße 3-4, 10115 Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hackbusch
authors.forename: André
authors.initials: A
authors.lastname: Dülsner
authors.forename: Nora
authors.initials: N
authors.lastname: Gatzke
authors.forename: Janine
authors.initials: J
authors.lastname: Krüger
authors.forename: Philipp
authors.initials: P
authors.lastname: Hillmeister
authors.forename: Stephanie
authors.initials: S
authors.lastname: Nagorka
authors.forename: Florian
authors.initials: F
authors.lastname: Blaschke
authors.forename: Zully
authors.initials: Z
authors.lastname: Ritter
authors.forename: Christa
authors.initials: C
authors.lastname: Thöne-Reineke
authors.forename: Frank-D
authors.initials: FD
authors.lastname: Böhmer
authors.forename: Ivo
authors.initials: I
authors.lastname: Buschmann
authors.forename: Kai
authors.initials: K
authors.lastname: Kappert
mesh_terms: D000818:Animals; D000077214:Becaplermin; D001921:Brain / Q000098:blood supply / Q000502:physiology; D017536:Carotid Artery, Common / Q000254:growth & development / Q000601:surgery; D002478:Cells, Cultured; D002941:Circle of Willis / Q000254:growth & development / Q000601:surgery; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis* / Q000378:metabolism; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3
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