Atherosclerosis 196 (2008) 240–247 Low dose apolipoprotein A-I rescues carotid arteries from inflammation in vivo Rajesh Puranik a,c , Shisan Bao a,b , Estelle Nobecourt a,1 , Stephen J. Nicholls a,2 , Gregory J. Dusting d , Philip J. Barter a,c , David S. Celermajer a,c , Kerry-Anne Rye a,c,e,∗ a The Heart Research Institute, Lipid Research Group 145, Missenden Road, Sydney, NSW 2050, Australia b Department of Pathology, University of Sydney, Australia c Department of Medicine, University of Sydney, Australia d Bernard O’Brien Institute of Microsurgery, University of Melbourne, Melbourne, Australia e Department of Medicine, University of Melbourne, Australia Received 21 March 2007; received in revised form 7 May 2007; accepted 11 May 2007 Available online 27 June 2007 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 9 h after collar insertion. The animals were sacrificed 24 h 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 3 h 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 9 h 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. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Acute inflammation; High density lipoproteins; Apolipoprotein A-I 1. Introduction High density lipoproteins (HDL) protect against the devel- opment of atherosclerosis [1]. There is emerging evidence ∗ Corresponding author. Tel.: +61 2 8208 8900; fax: +61 2 9565 5584. E-mail addresses: ryek@hri.org.au, karye@ozemail.com.au (K.-A. Rye). 1 Current address: INSERM U551, Paris, France. 2 Current address: Department of Cardiovascular Medicine, Cleveland Clinic Foundation, USA. that HDL also have additional beneficial properties, such as inhibiting endothelial cell and arterial inflammation in vitro and in vivo. In studies conducted in vitro, we and others have pre- viously shown that HDL inhibit expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin in human endothelial cells grown in culture [2]. HDL also inhibit the bind- ing of monocytes and neutrophils to cultured endothelial cells [3,4]. These anti-inflammatory properties of HDL are 0021-9150/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2007.05.008