title: Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions.
abstract: OBJECTIVE
  Cholesterol-rich nanoemulsions (LDE) bind to low-density lipoprotein (LDL) receptors and after injection into the bloodstream concentrate in aortas of atherosclerotic rabbits. Association of paclitaxel with LDE markedly reduces the lesions. In previous studies, treatment of refractory cancer patients with etoposide associated with LDE had been shown devoid of toxicity. In this study, the ability of etoposide to reduce lesions and inflammatory factors in atherosclerotic rabbits was investigated.
  
  
  METHODS
  Eighteen New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30, nine animals were treated with four weekly intravenous injections of etoposide oleate (6 mg/kg) associated with LDE, and nine control animals were treated with saline solution injections.
  
  
  RESULTS
  LDE-etoposide reduced the lesion areas of cholesterol-fed animals by 85% and intima width by 50% and impaired macrophage and smooth muscle cell invasion of the intima. Treatment also markedly reduced the protein expression of lipoprotein receptors (LDL receptor, LDL-related protein-1, cluster of differentiation 36, and scavenger receptor class B member 1), inflammatory cytokines (interleukin-1β and tumor necrosis factor-α), matrix metallopeptidase-9, and cell proliferation markers (topoisomerase IIα and tubulin).
  
  
  CONCLUSIONS
  The ability of LDE-etoposide to strongly reduce the lesion area and the inflammatory process warrants the great therapeutic potential of this novel preparation to target the inflammatory-proliferative basic mechanisms of the disease.
authors.affiliation: Heart Institute of Medical School Hospital (InCor), University of São Paulo, São Paulo, Brazil.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Tavares
authors.forename: Fatima R
authors.initials: FR
authors.lastname: Freitas
authors.forename: Jayme
authors.initials: J
authors.lastname: Diament
authors.forename: Raul C
authors.initials: RC
authors.lastname: Maranhão
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000008:administration & dosage* / Q000097:blood; D004435:Eating / Q000187:drug effects; D004655:Emulsions / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology* / Q000633:toxicity; D006651:Histocytochemistry; D007962:Leukocytes / Q000187:drug effects; D008074:Lipoproteins / Q000097:blood; D008297:Male; D049329:Nanostructures / Q000008:administration & dosage* / Q000633:toxicity; D011817:Rabbits; D011973:Receptors, LDL / Q000097:blood; D018675:Toxicity Tests
chemical_list: D004655:Emulsions; D008074:Lipoproteins; D011973:Receptors, LDL; D005047:Etoposide; D002784:Cholesterol
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