Stent-based controlled release of intravascular angiostatin to limit plaque progression and in-stent restenosis

Fumikiyo Ganaha, Edward Y. Kao, Humberto Wong, Christopher J. Elkins, Jane Lee, Shoreh Modanlou, Ceron Rhee, Michael D. Kuo, Eser Yuksel, Pamela N. Cifra, Jacob M. Waugh, Michael D. Dake

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


PURPOSE: To evaluate the importance of angiogenesis in plaque progression after stent placement, this study examines stent-based controlled delivery of the antiangiogenic agent, angiostatin, in a rabbit model. MATERIALS AND METHODS: Controlled release biodegradable microspheres delivering angiostatin or polymeronly microspheres (polylactic-co-glycolic-acid-polyethylene glycol; PLGA/PEG) were loaded in channeled stents, anchored, and deployed in the aorta of adult New Zealand white rabbits (n = 6 animals per group, three each per time point). The stented aortas were harvested at 7 days and 28 days and evaluated for neovascularization, local inflammation, vascular smooth muscle cell proliferation, and in-stent plaque progression. RESULTS: At 7 days, neovascularization was significantly decreased in the angiostatin groups (1.6 ± 1.6 neovessels per mm2 plaque) versus the control group (15.4 ± 2.6 neovessels per mm2 plaque; P = .00081), as were local inflammation where angiostatin-treated groups demonstrated significantly lower macrophage recruitment per cross section (34.9 ± 4.9 cells per cross section) relative to the control group (55.2 ± 3.84 cells per cross section; P = .0037). And a significant decrease in the overall vascular smooth muscle cell proliferation (143.8 ± 26.3 Ki-67 positive cells per mm 2) relative to the control group (263.2 ± 16.6 Ki-67 positive cells per mm2; P = .00074). At both 7 and 28 days, in-stent plaque progression in the angiostatin groups was successfully limited relative to the control group by 54% (0.255 ± 0.019% of cross section; P = .00016) and 19% (1.981 ± 0.080; P = .0033) respectively and resulted in reduction of in-stent restenosis relative to the control group. CONCLUSION: Angiostatin-eluting stents may limit neovascularity after arterial implantation, offer insight into in-stent restenosis, and allow future refinement of bioactive stent designs and clinical strategies, particularly in light of evidence that intimal smooth muscle cells may in part be marrow-derived.

Original languageEnglish (US)
Pages (from-to)601-608
Number of pages8
JournalJournal of Vascular and Interventional Radiology
Issue number6
StatePublished - Jun 2004

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine


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