Abstract 1047: Infusion of Reconstituted High Density Lipoproteins Into Humans Enhances the In Vitro Anti-Inflammatory Capacity of the High Density Lipoprotein Fraction.

Abstract

Background: Intravenous infusions of reconstituted high density lipoproteins (rHDL) have been shown to promote regression of coronary atheroma. Here we investigate the effects of rHDL infusion on the anti-inflammatory capacity of the isolated HDL fraction. Methods: Eight fasting Type 2 Diabetics (mean age 52 ± 2 years) received IV saline or apolipoprotein A-I (apoA-I)/phosphatidylcholine complexes (rHDL) at an apoA-I dose of 80mg/kg, on separate occasions in random order. The HDL fraction was isolated from subjects at baseline, 4 & 72hrs after infusion and assayed for chemical composition. The anti-inflammatory capacity of HDL preparations was assessed by incubation for 16hrs with human coronary artery endothelial cells. Cell expression of vascular cell adhesion molecule-1 (VCAM-1) and inter-cellular adhesion molecule (ICAM-1) 5 hrs after TNF-α stimulation was quantitated by flow cytometry. Results : Saline infusion had no effect on concentration or anti-inflammatory capacity of isolated HDL. rHDL infusion increased the concentration of HDL apoA-I (at baseline, 4h & 72h, [apoA-I] = 966 ± 105, 2562 ± 330 & 1701 ± 180 (ug/mL) respectively), as well as HDL cholesterol and HDL phospholipids. The addition of equivalent volumes of HDL (100uL) isolated at each time point inhibited VCAM-1 (Panel A) and ICAM-1 (Panel B) expression in proportion to the apoA-I concentration of the isolated HDL (p<0.01 ANOVA across time points for both VCAM-1/ICAM-1 expression and apoA-I concentration) (see figure ). Conclusions: Infusion of rHDL in humans increases the concentration of HDL apoA-I. The anti-inflammatory capacity of isolated HDL is enhanced in proportion to its apoA-I concentration.