title: Rapid change in plaque size, composition, and molecular footprint after recombinant apolipoprotein A-I Milano (ETC-216) administration: magnetic resonance imaging study in an experimental model of atherosclerosis.
abstract: OBJECTIVE
  This study sought to assess the effect of short-term apolipoprotein (apo) A-I(Milano) administration on plaque size and on suspected markers of plaque vulnerability.
  
  
  BACKGROUND
  Long-term lipid-lowering interventions can regress and stabilize atherosclerotic plaques. However, the majority of recurrent events occur early after the first episode. Interventions able to acutely induce plaque regression and stabilization are lacking. Regression of human coronary lesions after 5 weeks of treatment with apoA-I(Milano) administration has been shown. However, there are no data regarding its effect on plaque vulnerability.
  
  
  METHODS
  Advanced aortic lesions were induced in New Zealand White rabbits (n = 40). Plaque size was assessed by magnetic resonance imaging (MRI) at the end of atherosclerosis induction. Animals were randomized to placebo or apoA-I(Milano) phospholipids (ETC-216), 2 infusions 4 days apart. After the last dose, another MRI study was performed and aortas were processed for cellular composition and gene protein expression of markers associated with plaque instability.
  
  
  RESULTS
  Pre-treatment MRI showed similar plaque size in both groups, whereas post-treatment MRI showed 6% smaller plaques in apoA-I(Milano)-treated animals compared with placebo (p = 0.026). The apoA-I(Milano) treatment induced a 5% plaque regression (p = 0.003 vs. pre-treatment), whereas the placebo showed no significant effect. Plaque regression by apoA-I(Milano) was associated with a reduction in plaque macrophage density and a significant down-regulation in gene and protein expression of tissue factor, monocyte chemoattractant protein-1, and cyclooxygenase-2, as well as marked decrease in gelatinolytic activity. Conversely, cyclooxygenase-1 was significantly up-regulated.
  
  
  CONCLUSIONS
  Acute plaque regression observed after short-term apoA-I(Milano) administration was associated with a significant reduction in suspected makers of plaque vulnerability in an experimental model of atherosclerosis.
authors.affiliation: Cardiovascular Biology Research Laboratory, Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Borja
authors.initials: B
authors.lastname: Ibanez
authors.forename: Gemma
authors.initials: G
authors.lastname: Vilahur
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cimmino
authors.forename: Walter S
authors.initials: WS
authors.lastname: Speidl
authors.forename: Antonio
authors.initials: A
authors.lastname: Pinero
authors.forename: Brian G
authors.initials: BG
authors.lastname: Choi
authors.forename: M Urooj
authors.initials: MU
authors.lastname: Zafar
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Santos-Gallego
authors.forename: Brian
authors.initials: B
authors.lastname: Krause
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Badimon
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001018:Aortic Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000008:administration & dosage*; D050197:Atherosclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D008297:Male; D010713:Phosphatidylcholines / Q000008:administration & dosage*; D011817:Rabbits; D011897:Random Allocation
chemical_list: D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; C474616:ETC216; D010713:Phosphatidylcholines