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Updated: Jul 19, 2026
The Rabbit Model of Accelerated Atherosclerosis: A Methodological Perspective of the Iliac Artery Balloon Injury
Published on: October 3, 2017
Arsenic trioxide eluting stent reduces neointima formation in a rabbit iliac artery injury model
Wei Yang1, Junbo Ge, Hongling Liu
1Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Objective:
In-stent restenosis is caused by the neointimal hyperplasia, which involves abnormal growth of vascular smooth muscle cells (VSMC). Arsenic trioxide (As2O3) is known to be a potent inhibitor of cell proliferation. We therefore studied the role of an As2O3 eluting stent in the prevention of restenosis in a rabbit iliac artery model.
Methods And Results:
Bare stents, or stents coated with poly-L-lactic acid (PLLA) and either 40 microg of As2O3, 180 microg of paclitaxel or vehicle were implanted into the left proximal iliac arteries of New Zealand rabbits. The delivery of drugs from stents in vitro and in vivo was evaluated by atomic fluorescence spectrophotometry and high-performance liquid chromatography, respectively. Histomorphometric measurements at 7 or 28 days showed that, comparing to rabbits receiving the PLLA stent, in animals treated with As2O3 eluting or paclitaxel eluting stent neointima thickness was reduced by 50% and 46%, the absolute neointimal area was reduced by 53% and 44%, while the absolute luminal area was increased by 46% and 43%, respectively. There were no significant differences in injury or inflammation scores among PLLA, As2O3 eluting and paclitaxel eluting stents. As2O3 eluting stent induced more TUNEL-positiv VSMC than the other stents. As2O3 levels measured in the arterial tissue were much higher than those in serum, which were nearly undetectable at 7 days after stent implantation. In in vitro studies, cultured rabbit arterial VSMC were stimulated with As2O3 or paclitaxel and analyzed for their cell cycle progression and apoptosis by flow cytometry and electron microscopy. As2O3 treatment resulted in a reduction of VSMC number in G1 phase with a concomitant increase in apoptosis of VSMC, whereas paclitaxel treatment led to blocking of VSMC in the G2/M phase.
Conclusion:
In a rabbit iliac artery model PLLA coated As2O3 eluting stent significantly suppressed in-stent restenosis by reducing proliferation and inducing apoptosis of VSMC.
