Abstract 1724: The Effects of ApolipoproteinA-I Infusions on the Distribution and Anti-Inflammatory Capacity of High Density Lipoproteins in the Rabbit
Infusions of apolipoprotein (apoA-I) in the lipid-free or lipid-associated form inhibit acute vascular inflammation in rabbits. Here, we investigate how these infusions affect endogenous HDL distribution and whether they enhance the anti-inflammatory capacity of the total HDL fraction. Rabbits (n = 3/group) were infused with saline or with 125I-labelled apoA-I (8mg/kg) in the lipid-free form or as a constituent of discoidal reconstituted HDL (rHDL). Serial blood samples were collected at 1–360 min post-infusion. Plasma was isolated and subjected to 2-D gel electrophoresis. Distributions of endogenous apoA-I and 125I-labelled apoA-I were determined by immunoblotting and phosphorimaging, respectively. HDL were ultracentrifugally isolated from plasma at 5 and at 360 min post-infusion and their anti-inflammatory capacity was assessed by quantitating vascular cell adhesion molecule-1(VCAM-1) and intercellular adhesion molecule-1(ICAM-1) protein expression in TNF-α-activated human coronary artery endothelial cells. At 1 min post-infusion, 74 ± 1% of the lipid-free 125I-labelled apoA-I and 25 ± 2% of the lipid-associated 125I-labelled apoA-I had been cleared from the circulation. The remaining 125I-labelled apoA-I rapidly co-migrated with the endogenous HDL. Irrespective of whether the animals were infused with lipid-free apoA-I or rHDL, HDL size increased transiently at 5 min post-infusion. The ultracentrifugally isolated HDL inhibited VCAM-1 and ICAM-1 expression in a concentration dependent manner. Relative to the saline-infused animals, the anti-inflammatory capacity of the HDL from the animals infused with lipid-free apoA-I or rHDL was mildly enhanced at 5, but not at 360 min post-infusion.
Lipid-free apoA-I is cleared from the circulation more rapidly than lipid-associated apoA-I,
the infused lipid-free and lipid-associated apoA-I that remains in the plasma rapidly co-migrates with endogenous HDL which transiently increases in size, and
the profound inhibition of acute vascular inflammation that was previously observed following infusion of apoA-I into rabbits is unlikely to be explained by changes in the anti-inflammatory capacity of the HDL fraction.