Thalidomide influences atherogenesis in aortas of ApoE(-/-)/LDLR (-/-) double knockout mice: a nano-CT study.
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 mm(2), p < 0.001). Cross sectional area of plaque decreased significantly when treated with thalidomide (0.57 ± 0.0187 vs. 0.803 ± 0.0148 mm(2), 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.
Department of Diagnostic and Interventional Radiology, University Hospital Giessen, Klinikstrasse 33, 35385, Giessen, Germany, marian.kampschulte@radiol.med.uni-giessen.de.
Marian
M
Kampschulte
Irina
I
Gunkel
Philipp
P
Stieger
Daniel G
DG
Sedding
Anne
A
Brinkmann
Erik L
EL
Ritman
Gabriele A
GA
Krombach
Alexander C
AC
Langheinrich
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001027:Aortography / Q000379:methods*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D036103:Nanotechnology / Q000379:methods*; D009389:Neovascularization, Pathologic; D058226:Plaque, Atherosclerotic; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D013792:Thalidomide / Q000494:pharmacology*; D013997:Time Factors; D014057:Tomography, X-Ray Computed / Q000379:methods*
D020533:Angiogenesis Inhibitors; D001057:Apolipoproteins E; D011973:Receptors, LDL; D013792:Thalidomide