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BioMed Research International
Volume 2013 (2013), Article ID 802149, 9 pages
Research Article

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

1Center for Cardiovascular Research (CCR), Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité-University Medicine Berlin, Hessische Straße 3-4, 10115 Berlin, Germany
2Department of Internal Medicine, Cardiology and Angiology, Richard Thoma Laboratories for Arteriogenesis, Center for Cardiovascular Research, Charité-University Medicine Berlin, Hessische Straße 3-4, 10115 Berlin, Germany
3Department of Cardiology, Charité-University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
4Clinic for Radiology and Nuclear Medicine, Charité-University Medicine Berlin, Center for Muscle and Bone Research, Free University Berlin, Hindenburgdamm 30, 12203 Berlin, Germany
5Center for Cardiovascular Research (CCR), and Department of Experimental Medicine, Charité-University Medicine Berlin, Hessische Straße 3-4, 10115 Berlin, Germany
6Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital, Hans-Knöll-Straße 3-4, 07745 Jena, Germany

Received 25 April 2013; Revised 27 June 2013; Accepted 17 July 2013

Academic Editor: Goutam Ghosh Choudhury

Copyright © 2013 Daniel Hackbusch et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.