title: Low dose apolipoprotein A-I rescues carotid arteries from inflammation in vivo.
abstract: This study investigates the ability of a single, low dose of apolipoprotein (apo) A-I, the main lipoprotein of high density lipoproteins (HDL), to inhibit acute vascular inflammation in normocholesterolemic New Zealand White rabbits. Acute vascular inflammation was induced in the animals by placing a non-occlusive, silastic collar around the left common carotid artery. The animals (n=5/group) received a single, low dose infusion of saline or lipid-free apoA-I at the time of, or 3 or 9h after collar insertion. The animals were sacrificed 24h post-collar insertion. Inflammatory markers in the artery wall were quantitated immunohistochemically. The saline-treated animals exhibited substantial pan-arterial inflammation, which was inhibited by a single apoA-I infusion (2 or 8 mg/kg) at the time of collar insertion. A single 8 mg/kg infusion of lipid-free apoA-I administered 3h post-collar insertion reduced neutrophil recruitment into the vessel wall, and MPO expression, as well as endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by >85% (p<0.01 for all). A single 8 mg/kg infusion of lipid-free apoA-I administered 9h after collar insertion decreased VCAM-1 expression, neutrophil infiltration and MPO expression by 88% (p<0.001), 47% (p<0.01), and 90% (p<0.01), respectively. This indicates that a single low dose infusion of apoA-I administered after the onset of acute inflammation in carotid arteries decreases neutrophil infiltration and inhibits neutrophil and endothelial cell activation. These findings have potential implications for treating acute vascular inflammation in conditions such as acute coronary and stroke syndromes.
authors.affiliation: The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia; Department of Medicine, University of Sydney, Australia.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Puranik
authors.affiliation: The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia; Department of Pathology, University of Sydney, Australia.
authors.forename: Shisan
authors.initials: S
authors.lastname: Bao
authors.affiliation: The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia.
authors.forename: Estelle
authors.initials: E
authors.lastname: Nobecourt
authors.affiliation: The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.affiliation: Bernard O'Brien Institute of Microsurgery, University of Melbourne, Melbourne, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
authors.affiliation: The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia; Department of Medicine, University of Sydney, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.affiliation: The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia; Department of Medicine, University of Sydney, Australia.
authors.forename: David S
authors.initials: DS
authors.lastname: Celermajer
authors.affiliation: The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia; Department of Medicine, University of Sydney, Australia; Department of Medicine, University of Melbourne, Australia. Electronic address: ryek@hri.org.au.
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage*; D002340:Carotid Artery Diseases / Q000188:drug therapy*; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy*; D007262:Infusions, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000008:administration & dosage*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase