title: Plaque stabilizing effects of apolipoprotein A-IV.
abstract: Apolipoprotein (apo) A-IV, the third most abundant HDL-associated protein, is atheroprotective and shares similar properties as apoA-I. We have reported previously that apoA-I, the most abundant apolipoprotein in HDL, inhibits plaque disruption in a mouse model. We aimed at examining the effects of apoA-IV on markers of plaque stability in vivo.
  
  
  
  Plaques within brachiocephalic arteries of 16-week old apoE-knockout C57BL/6 mice were examined for changes in composition after 10 weeks on a high-fat diet (HFD). The animals received twice-weekly injections of human lipid-free apoA-IV (1 mg/kg, n = 31) or PBS (n = 32) during the 9th and 10th weeks of the HFD.
  
  
  
  In the apoA-IV treated mice, there were significantly fewer hemorrhagic plaque disruptions (9/31 vs. 18/32, p < 0.05), thicker fibrous caps, smaller lipid cores, a lower macrophage:SMC ratio, less MMP-9 protein, more collagen, and fewer proliferating cells. In the plaques of mice given apoA-IV, MCP-1, VCAM-1, and inducible NOS were also significantly lower. Based on the percentage of cleaved PARP-positive and TUNEL-positive plaque nuclei, apoA-IV reduced apoptosis. in HMDMs, apoA-IV reduced MMP-9 mRNA expression by half, doubled mRNA levels of TIMP1 and decreased MMP-9 activity.
  
  
  
  ApoA-IV treatment is associated with a more stable plaque phenotype and a reduced incidence of acute disruptions in this mouse model.
authors.affiliation: The Heart Research Institute, Sydney, Australia. Electronic address: FrancisRuel.Geronimo@uts.edu.au.
authors.forename: F R B
authors.initials: FRB
authors.lastname: Geronimo
authors.affiliation: School of Medical Sciences, University of New South Wales, Australia. Electronic address: p.barter@unsw.edu.au.
authors.forename: P J
authors.initials: PJ
authors.lastname: Barter
authors.affiliation: School of Medical Sciences, University of New South Wales, Australia. Electronic address: k.rye@unsw.edu.au.
authors.forename: K A
authors.initials: KA
authors.lastname: Rye
authors.affiliation: The Heart Research Institute, Sydney, Australia; School of Medical Sciences, University of Otago, Dunedin, New Zealand. Electronic address: alison.heather@otago.ac.nz.
authors.forename: A K
authors.initials: AK
authors.lastname: Heather
authors.affiliation: School of Dentistry, University of Western Australia, Australia. Electronic address: kate.shearston@uwa.edu.au.
authors.forename: K D
authors.initials: KD
authors.lastname: Shearston
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology, Sydney, Australia. Electronic address: Kenneth.Rodgers@uts.edu.au.
authors.forename: K J
authors.initials: KJ
authors.lastname: Rodgers
mesh_terms: D000818:Animals; D001054:Apolipoproteins A / Q000097:blood*; D017209:Apoptosis; D001158:Arteries / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism; D059305:Diet, High-Fat; D006801:Humans; D007249:Inflammation; D008075:Lipoproteins, HDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE; D018384:Oxidative Stress; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001054:Apolipoproteins A; D008075:Lipoproteins, HDL; D019010:Vascular Cell Adhesion Molecule-1; C022205:apolipoprotein A-IV; D020780:Matrix Metalloproteinase 9
keywords: Acute coronary syndromes; Animal models of human disease; Apoptosis; Atherosclerosis; Inflammation; Lipid and lipoprotein metabolism; Lipoproteins; Matrix metalloproteinase; Mechanism of atherosclerosis