title: Macrophage depletion by clodronate-containing liposomes reduces neointimal formation after balloon injury in rats and rabbits.
abstract: 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.
  
  
  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-1beta 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.
authors.affiliation: Department of Cardiology, Hadassah-Hebrew University Hospital, Jerusalem, Israel. danen@md2.huji.ac.il
authors.forename: Haim D
authors.initials: HD
authors.lastname: Danenberg
authors.forename: Ilia
authors.initials: I
authors.lastname: Fishbein
authors.forename: Jianchuan
authors.initials: J
authors.lastname: Gao
authors.forename: Jukka
authors.initials: J
authors.lastname: Mönkkönen
authors.forename: Reuven
authors.initials: R
authors.lastname: Reich
authors.forename: Irith
authors.initials: I
authors.lastname: Gati
authors.forename: Evgeny
authors.initials: E
authors.lastname: Moerman
authors.forename: Gershon
authors.initials: G
authors.lastname: Golomb
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002404:Catheterization / Q000009:adverse effects*; D002455:Cell Division / Q000187:drug effects; D004002:Clodronic Acid / Q000008:administration & dosage* / Q000737:chemistry; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008081:Liposomes; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D017539:Tunica Intima / Q000187:drug effects* / Q000293:injuries / Q000473:pathology
chemical_list: D007375:Interleukin-1; D018950:Lipopolysaccharide Receptors; D008081:Liposomes; D018809:Proliferating Cell Nuclear Antigen; D004002:Clodronic Acid; D020778:Matrix Metalloproteinase 2