3-Deazaadenosine inhibits vasa vasorum neovascularization in aortas of ApoE-/-/LDL-/- double knockout mice

Alexander C. Langheinrich, Daniel G. Sedding, Marian Kampschulte, Regina Moritz, Jochen Wilhelm, Werner G. Haberbosch, Erik L. Ritman, Rainer M. Bohle

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: Atherosclerosis and inflammation/angiogenesis are strongly associated including growth of vasa vasorum (VV) and plaque neovascularization, but a causative role for neovascularization has still not been established. Hence, we investigated the effect of 3-deazaadenosine (c3Ado), an anti-inflammatory and anti-proliferative drug, on plaque progression and VV neovascularization in apoE-/-/LDL-/- double knockout mice. Methods: The arterial trees from apoE-/-/LDL-/- mice with, or without c3Ado at the age of 16 weeks (n = 10), 18 weeks (n = 8) and 20 weeks (n = 7) were infused in situ with Microfil, and the aortas harvested and scanned with micro-CT (12 μm cubic voxel). We characterized plaque volume and VV luminal volume along the descending aorta using Analyze 6.0 software. Cellular effects of c3Ado on human endothelial and vascular smooth muscle cells were investigated in cell cultures and on nylon cDNA expression arrays. Results: Lesions spatially connected to VV increased from 16 to 20 weeks significantly (p < 0.001). The volume of atherosclerotic lesions was significantly reduced in animals treated with c3Ado (p < 0.01). This was accompanied by a significant decrease of vasa vasorum neovascularization along the descending aorta (p < 0.01). Using nylon cDNA expression arrays, we identified the regulation of anti-proliferative, anti-inflammatory genes in human smooth muscle cells which might be involved in the anti-angiogenic effects of c3Ado. Moreover, c3Ado dose-dependently prevented the proliferation and migration of human coronary artery endothelial cells in vitro. Conclusion: The smaller lesion volume in animals treated with c3Ado was closely associated with a reduced VV neovascularization, suggesting a direct relationship between lesion growth and VV development.

Original languageEnglish (US)
Pages (from-to)103-110
Number of pages8
JournalAtherosclerosis
Volume202
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • 3-Deazaadenosine
  • Angiogenesis
  • Atherosclerosis
  • Micro-CT
  • Vasa vasorum

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of '3-Deazaadenosine inhibits vasa vasorum neovascularization in aortas of ApoE<sup>-/-</sup>/LDL<sup>-/-</sup> double knockout mice'. Together they form a unique fingerprint.

  • Cite this

    Langheinrich, A. C., Sedding, D. G., Kampschulte, M., Moritz, R., Wilhelm, J., Haberbosch, W. G., Ritman, E. L., & Bohle, R. M. (2009). 3-Deazaadenosine inhibits vasa vasorum neovascularization in aortas of ApoE-/-/LDL-/- double knockout mice. Atherosclerosis, 202(1), 103-110. https://doi.org/10.1016/j.atherosclerosis.2008.04.008