Knockout of Density-Enhanced Phosphatase-1 Impairs Cerebrovascular Reserve Capacity in an Arteriogenesis Model in Mice

• Published in: BioMed research international Vol. 2013; no. 2013; pp. 1 - 9
• Main Authors: Böhmer, Frank-D., Buschmann, Ivo, Kappert, Kai, Ritter, Zully, Blaschke, Florian, Nagorka, Stephanie, Hillmeister, Philipp, Krüger, Janine, Gatzke, Nora, Dülsner, André, Hackbusch, Daniel, Thöne-Reineke, Christa
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2013; Hindawi Limited
• Subjects: Animals; Biomedical research; Brain - blood supply; Brain - physiology; Carotid Artery, Common - growth & development; Carotid Artery, Common - surgery; Cell growth; Cells, Cultured; Circle of Willis - growth & development; Circle of Willis - surgery; Gene expression; Gene Expression Regulation; Humans; Kinases; Medicine; Mice; Mice, Knockout; Neovascularization, Physiologic - genetics; Phosphorylation; Proto-Oncogene Proteins c-sis - biosynthesis; Proto-Oncogene Proteins c-sis - metabolism; Receptor-Like Protein Tyrosine Phosphatases, Class 3 - genetics; Receptor-Like Protein Tyrosine Phosphatases, Class 3 - metabolism; Rodents; Signal Transduction; Studies; Vascular endothelial growth factor; Veins & arteries
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2013/802149

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.