Macrophage Depletion by Clodronate-Containing Liposomes Reduces Neointimal Formation After Balloon Injury in Rats and Rabbits
| Autor: | Reuven Reich, Evgeny Moerman, Jukka Mönkkönen, Jianchuan Gao, Irith Gati, Haim D. Danenberg, Ilia Fishbein, Gershon Golomb |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Pathology medicine.medical_specialty genetic structures Lipopolysaccharide Receptors Inflammation Pharmacology behavioral disciplines and activities Monocytes Catheterization Restenosis Proliferating Cell Nuclear Antigen Physiology (medical) Animals Medicine Carotid Stenosis Neointimal hyperplasia business.industry Vascular disease Cell growth Macrophages Rats Inbred Strains Flow Cytometry medicine.disease Immunohistochemistry Pathophysiology Rats Disease Models Animal Carotid Arteries medicine.anatomical_structure Liver nervous system Liposomes Matrix Metalloproteinase 2 Clodronic acid Rabbits Clodronic Acid medicine.symptom Tunica Intima Cardiology and Cardiovascular Medicine business Cell Division Spleen psychological phenomena and processes Interleukin-1 Artery medicine.drug |
| Zdroj: | Circulation. 106:599-605 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.0000023532.98469.48 |
| Popis: | Background — Inflammation is critical to vascular repair after mechanical injury. Excessive inflammation enhances neointimal formation and restenosis. We examined whether transient systemic inactivation of macrophages at the time of vascular intervention could attenuate the degree of expected restenosis. Methods and Results — Liposomal clodronate (LC) inhibited the growth of cultured macrophages but had no effect on endothelial or smooth muscle cells and suppressed neointimal hyperplasia in hypercholesterolemic rabbits and rats after intravenous administration of LC, with no adverse effects. LC treatment reduced the number of blood monocytes and decreased macrophage infiltration in the injured arteries as well as smooth muscle cell proliferation, interleukin-1β transcription, and production and matrix metalloproteinase-2 activity. Conclusions — Macrophages play a pivotal role in vascular repair after mechanical arterial injury. Systemic inactivation and depletion of monocytes and macrophages by LC reduce neointimal hyperplasia and restenosis. |
| Databáze: | OpenAIRE |
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