Thalidomide influences atherogenesis in aortas of ApoE-/-/ LDLR-/- double knockout mice: A nano-CT study

Marian Kampschulte, Irina Gunkel, Philipp Stieger, Daniel G. Sedding, Anne Brinkmann, Erik L. Ritman, Gabriele A. Krombach, Alexander C. Langheinrich

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Plaque progression in atherosclerosis is closely connected to angiogenesis due to vasa vasorum (VV) growth. Objective of this study was to determine the unknown long-term effect of thalidomide on adventitial VV neovascularization and plaque progression using nano-focussed computed tomography (nano-CT). Proliferation and migration assays in human coronary artery endothelial cells (HCAEC) measured number of viable cells after incubation with thalidomide. Male ApoE-/-/LDLR-/- (AL) mice (n = 5) received a thalidomide containing western diet (WD) over 29 weeks. Another five male AL mice (WD without thalidomide) served as control group. Descending aortas were scanned with nano-CT at (1.5 μm)3 isotropic voxel size. Number and area of adventitial VV as well as plaque cross sectional area were measured. Results were complemented by histology. Thalidomide inhibited proliferation and migration of HCAEC dose-dependently. VV neovascularization decreased in number per cross section (7.66 ± 0.301 vs. 8.62 ± 0.164, p < 0.001) and in cross sectional area (0.0183 ± 0.0011 vs. 0.0238 ± 0.0008 mm2, p < 0.001). Cross sectional area of plaque decreased significantly when treated with thalidomide (0.57 ± 0.0187 vs. 0.803 ± 0.0148 mm2, p < 0.001). Nano-CT imaging revealed a reduced plaque growth and VV neovascularization after long-term application of thalidomide. Therefore, nano-CT can be considered as a new method to detect therapeutic effects in experimental models of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)795-802
Number of pages8
JournalInternational Journal of Cardiovascular Imaging
Volume30
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • Angiogenesis
  • Atherosclerosis
  • Nano-CT
  • Thalidomide
  • Vasa vasorum

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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    Kampschulte, M., Gunkel, I., Stieger, P., Sedding, D. G., Brinkmann, A., Ritman, E. L., Krombach, G. A., & Langheinrich, A. C. (2014). Thalidomide influences atherogenesis in aortas of ApoE-/-/ LDLR-/- double knockout mice: A nano-CT study. International Journal of Cardiovascular Imaging, 30(4), 795-802. https://doi.org/10.1007/s10554-014-0380-5