Liposomal Alendronate Inhibits Systemic Innate Immunity and Reduces In-Stent Neointimal Hyperplasia in Rabbits
Abstract
Background— Innate immunity is of major importance in vascular repair. The present study evaluated whether systemic and transient depletion of monocytes and macrophages with liposome-encapsulated bisphosphonates inhibits experimental in-stent neointimal formation. Methods and Results— Rabbits fed on a hypercholesterolemic diet underwent bilateral iliac artery balloon denudation and stent deployment. Liposomal alendronate (3 or 6 mg/kg) was given concurrently with stenting. Monocyte counts were reduced by >90% 24 to 48 hours after a single injection of liposomal alendronate, returning to basal levels at 6 days. This treatment significantly reduced intimal area at 28 days, from 3.88±0.93 to 2.08±0.58 and 2.16±0.62 mm 2 . Lumen area was increased from 2.87±0.44 to 3.57±0.65 and 3.45±0.58 mm 2 , and arterial stenosis was reduced from 58±11% to 37±8% and 38±7% in controls, rabbits treated with 3 mg/kg, and rabbits treated with 6 mg/kg, respectively (mean±SD, n=8 rabbits/group, P <0.01 for all 3 parameters). No drug-related adverse effects were observed. Reduction in neointimal formation was associated with reduced arterial macrophage infiltration and proliferation at 6 days and with an equal reduction in intimal macrophage and smooth muscle cell content at 28 days after injury. Conversely, drug regimens ineffective in reducing monocyte levels did not inhibit neointimal formation. Conclusions— Systemic transient depletion of monocytes and macrophages, by a single liposomal bisphosphonates injection concurrent with injury, reduces in-stent neointimal formation and arterial stenosis in hypercholesterolemic rabbits.
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In hypercholesterolaemic rabbits, a single dose of liposomal alendronate concurrent with stent implantation resulted in reduced in-stent neointimal formation and arterial stenosis.
“hypercholesterolaemic rabbits were injected with a single dose of liposomal alendronate (a more potent bisphosphonate than clodronate), concurrent with stent implantation, which resulted in reduced in-stent neointimal formation and arterial stenosis90 (FIG. 2c).”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [90]
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Perspectives and opportunities for nanomedicine in the management of atherosclerosis
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- Authors
- Danenberg, H. D., Golomb, G., Groothuis, A., Gao, J., Epstein, H., Swaminathan, R. V., Seifert, P., & Edelman, E. R.
- Affiliations
- Hebrew University of Jerusalem (IL)
- From the Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Mass (H.D.D., A.G., R.V.S., P.S., E.R.E.); and the Department of Cardiology, Hadassah University Hospital (H.D.D.), and School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem (G.G., J.G., H.E.), Jerusalem, Israel.
- ORCID
- Venue
- Circulation
- Published
- 2003-12-02
- Volume
- 108
- Issue
- 22
- Pages
- 2798-2804
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2169904202
- Cited by
- 104
- References
- 35
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 4 · 2015: 2 · 2014: 6 · 2013: 4 · 2012: 8
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Hebrew University of Jerusalem
- Israel Science Foundation
- National Institutes of Health (HL-49039)
- David R. Bloom Center for Pharmacy, Hebrew University of Jerusalem
- National Heart, Lung, and Blood Institute (HL 60407, R01HL060407)
- National Institute of General Medical Sciences (GM/HL49039)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Coronary Interventions and Diagnostics
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Keywords
- bisphosphonates, intimal hyperplasia, in-stent restenosis, innate immunity, monocyte depletion, macrophage depletion, vascular repair, arterial stenosis, smooth muscle cell proliferation, hypercholesterolemic rabbits, balloon denudation
- MeSH terms
- Animals, Cell Count, Cell Division, Cell Movement, Diet, Atherogenic, Disease Models, Animal, Graft Occlusion, Vascular, Hyperplasia, Iliac Artery, Immunity, Innate, Leukocyte Count, Liposomes, Macrophages, Monocytes, Muscle, Smooth, Vascular, Rabbits, Stents, Tunica Intima, Alendronate
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