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(Circulation. 2005;111:1543-1550.)
© 2005 American Heart Association, Inc.

Vascular Medicine

Reconstituted High-Density Lipoproteins Inhibit the Acute Pro-Oxidant and Proinflammatory Vascular Changes Induced by a Periarterial Collar in Normocholesterolemic Rabbits

Stephen J. Nicholls, MBBS, PhD, FRACP; Gregory J. Dusting, PhD; Belinda Cutri, BMedSc (Hons); Shisan Bao, MBBS, PhD; Grant R. Drummond, PhD; Kerry-Anne Rye, PhD; Philip J. Barter, MBBS, PhD, FRACP

From the Heart Research Institute, Sydney (S.J.N., B.C., K.-A.R., P.J.B., S.B.); the Department of Medicine, University of Adelaide, Adelaide (S.J.N.); the Howard Florey Institute, University of Melbourne, Melbourne (G.J.D., G.R.D.); the Department of Medicine, University of Sydney, Sydney (P.J.B.); and the Department of Pathology, University of Sydney, Sydney (S.B.), Australia.

Correspondence to Professor Philip Barter, The Heart Research Institute, 145 Missenden Rd, Camperdown, NSW 2050, Australia. E-mail p.barter{at}hri.org.au

Received August 12, 2004; revision received November 15, 2004; accepted December 13, 2004.

Background— HDLs have antiinflammatory and antioxidant properties in vitro. This study investigates these properties in vivo.

Methods and Results— Chow-fed, normocholesterolemic New Zealand White rabbits received a daily infusion of (1) saline, (2) reconstituted HDL (rHDL) containing 25 mg apolipoprotein (apo) A-I and 50 mg of either 1-palmitoyl-2-linoleoyl phosphatidylcholine (PLPC) or 1,2-dipalmitoyl phosphatidylcholine (DPPC), (3) 25 mg lipid-free apoA-I, or (4) 50 mg of either PLPC-small unilamellar vesicles (SUVs) or DPPC-SUVs on each of 3 consecutive days. Nonocclusive carotid periarterial collars were implanted after the second dose of treatment. Forty-eight hours after insertion of the collars, the arteries were removed and analyzed for the presence of reactive oxygen species, the infiltration of neutrophils, and the expression of adhesion proteins and chemokines. Insertion of the periarterial collar induced a 4.1-fold increase in presence of vascular wall reactive oxygen species. This effect was completely abolished in the animals infused with rHDL. The periarterial collar was associated with a dense infiltration of the arterial wall by polymorphonuclear leukocytes. This infiltration was inhibited by 73% to 94% in the animals infused with rHDL, by 75% in the animals infused with lipid-free apoA-I, and by 51% to 65% in animals infused with SUVs. There were no significant differences between the effects of PLPC and DPPC in either the rHDL or SUVs. Endothelial expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 was also increased by the collar insertion and inhibited by rHDL, lipid-free apoA-I, and, to a lesser extent, also by the SUVs.

Conclusions— Infusion of rHDL, apoA-I, and phospholipid-SUVs inhibits the early pro-oxidant and proinflammatory changes induced by a periarterial collar in normocholesterolemic rabbits.

Key Words: lipoproteins • inflammation • cholesterol • antioxidants • endothelium

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