title: Inhibition of rupture of established atherosclerotic plaques by treatment with apolipoprotein A-I.
abstract: OBJECTIVE
  Plasma concentrations of high-density lipoprotein (HDL)-cholesterol correlate inversely with the incidence of myocardial infarction in humans. We investigated the effect of treatment with human apolipoprotein A-I (apoA-I), the principal protein of HDL, on plaque disruption in an animal model.
  
  
  RESULTS
  Seventy apolipoprotein E knockout mice were induced to develop atherosclerotic lesions in the brachiocephalic artery by feeding a high-fat diet for 9 weeks. Mice then received twice-weekly treatment with human apoA-I (8 mg/kg) or vehicle, for 2 weeks. The incidence of acute plaque disruption was reduced by 65% in mice receiving apoA-I (P < 0.01). Plaques in treated mice had a more stable phenotype, with an increase in smooth muscle cell (SMC): macrophage ratio (P = 0.05), principally the consequence of an increase in the number of SMC in plaques. In the fibrous cap, there were reductions in matrix metalloproteinase-13 (-69%, P < 0.0001) and S100A4, a marker of SMC de-differentiation (-60%, P < 0.0001). These results indicate that 2 weeks of treatment with small amounts of human apoA-I produces more stable plaques in a mouse model.
  
  
  CONCLUSIONS
  Treatment with apoA-I has the potential to stabilize plaques and prevent plaque rupture in humans.
authors.affiliation: The Heart Research Institute, 7 Eliza Street, Newtown NSW 2042, Australia.
authors.forename: Gerrit J
authors.initials: GJ
authors.lastname: Reimers
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Jackson
authors.forename: Jasmine
authors.initials: J
authors.lastname: Rickards
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Chan
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Cohn
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Rodgers
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016122:Brachiocephalic Trunk / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D054337:Cell Dedifferentiation; D008076:Cholesterol, HDL / Q000097:blood; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012422:Rupture, Spontaneous; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D002317:Cardiovascular Agents; D008076:Cholesterol, HDL; D018836:Inflammation Mediators; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D003094:Collagen; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse