Factors Influencing the Ability of HDL to Inhibit Expression of Vascular Cell Adhesion Molecule-1 in Endothelial Cells

Abstract

We have previously reported that high density lipoproteins (HDLs) inhibit the cytokine-induced expression of adhesion molecules in endothelial cells. Here we investigate whether different preparations of HDLs vary in their ability to inhibit the expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) activated by tumor necrosis factor-alpha (TNF-alpha). HDLs collected from a number of different human subjects all inhibited VCAM-1 expression in a concentration-dependent manner, although the extent of inhibition varied widely between subjects. The inhibitory activities of the HDL2 and HDL3 subfractions isolated from individual subjects also differed. Whether equated for concentrations of apolipoprotein (apo) A-I or cholesterol, the inhibitory activity of HDL3 was superior to that of HDL2. This difference remained apparent even when the HDL subfractions were present only during preincubations with the HUVECs and were removed before activation by TNF-alpha. To determine whether the inhibitory effect of HDL3 was influenced by apolipoprotein composition, preparations of HDL3 were modified by replacing all of their apo A-I with apo A-II. This change in apolipoprotein composition had no effect on the ability of the HDL3 to inhibit endothelial VCAM-1 expression. Thus, it has been shown that different preparations of HDLs differ markedly in their abilities to inhibit VCAM-1 expression in cytokine-activated HUVECs. The mechanism underlying the differences remains to be determined.

Intravascular Free Tissue Factor Pathway Inhibitor Is Inversely Correlated With HDL Cholesterol and Postheparin Lipoprotein Lipase but Proportional to Apolipoprotein A-II

“…36 It has been elucidated that HDL improves endothelial function by opposing oxidation 16 -18 and expression of adhesion molecules. 19 We postulate that the inverse relationship between HDL-C and preheparin and postheparin free TFPI in the present CAD patients also reflects compensatory augmentation of antithrombotic properties of the vascular wall to maintain normal endothelial function.…”

Antioxidative Activity of HDL Particle Subspecies Is Impaired in Hyperalphalipoproteinemia: Relevance of Enzymatic and Physicochemical Properties

“…10 Small, dense, lipid-poor HDL3 display higher capacity to accept cholesterol, 11 to inhibit expression of adhesion molecules on endothelial cells in vitro, 12 and to protect LDL from oxidative stress [13][14][15] as compared with large, light, lipid-rich HDL2. The intravascular metabolism and particle heterogeneity of HDL are altered in HALP.…”

Identification of a Sequence of Apolipoprotein A-I Associated with the Activation of Lecithin:Cholesterol Acyltransferase

“…Lipid-free and lipid-bound apoA-I are efficient acceptors of cholesterol released from the cell plasma membrane (9,10). ApoA-I regulates the translocation of intracellular cholesterol to the plasma membrane (11,12), promotes efflux of intracellular cholesterol (13)(14)(15)(16), triggers signaling pathways that could be related to cholesterol efflux (17)(18)(19), and regulates expression of adhesion molecules (20). Many of these activities are related to the unique secondary structure of apoA-I: when bound to lipid, apoA-I consists of nine 22-mer and two 11-mer amphipathic ␣-helices spanning almost the entire length of apoA-I (21).…”