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

Abstract

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

High-density lipoproteins: an emerging target in the prevention of cardiovascular disease

“…HDL was recently demonstrated to possess antiinflammatory properties in a normocholesterolaemic model of acute vascular inflammation [30]. The vascular infiltration by neutrophils and endothelial expression of adhesion molecules stimulated by application of a periarterial collar was markedly attenuated by infusion of rHDL to chow-fed rabbits ( Figure 3).…”

“…The finding that HDLs possess a number of antioxidant factors, including paraoxonase and platelet-activating factor -acetylhydrolase [27], and are the major in vivo sink for lipid hydroperoxides [28], provides a number of potential mechanisms by which oxidative modification of LDL is impaired. Administration of HDL in both cellular [29] and animal [30] settings has also been reported to inhibit the generation of reactive oxygen species, such as superoxide, and restore its physiological balance to nitric oxide (NO) (Figure 2). …”

HDL and Atherothrombotic Vascular Disease

“…For example, a single injection of discoidal rHDL particles in pigs prevented upregulation of E-selectin expression in response to intradermal interleukin-1α (Cockerill et al 2001). Moreover, daily treatment of normocholesterolemic rabbits with rHDLs or lipid-free apoA-I markedly attenuated periarterial collar-induced endothelial expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 as well as concomitant neutrophil infiltration into the vessel wall and generation of ROS (Nicholls et al 2005). The positive effects of lipid-free apoA-I on pro-inflammatory vascular changes were still observed when administered as a single low dose 3 h after insertion of the non-occlusive periarterial collar (Puranik et al 2008), indicating that infusion of apoA-I may also be able to rescue preestablished vascular inflammation.…”

High-Density Lipoprotein

“…27,[60][61][62] Furthermore, it suppresses the expression of adhesion molecules, such as vascular cell adhesion molecule 1, and inhibits the adhesion of white blood cells. 25,63 HDL also exerts antithrombotic effects because it reduces tissue factor expression in endothelial cells exposed to cytokines and reduces platelet activation. 64 Furthermore, in the mouse carotid artery model, HDL enhances endothelial repair after vascular injury.…”