Lack of inhibitory effect of HDL on TNFalpha-induced adhesion molecule expression in human aortic endothelial cells

• Published in: Atherosclerosis Vol. 165; no. 2; pp. 241 - 249
• Main Authors: Zhang, Wei Jian, Stocker, Roland, McCall, Mark R, Forte, Trudy M, Frei, Balz
• Format: Journal Article
• Language: English
• Published: Ireland 01.12.2002
• Subjects: Blotting, Northern; E-Selectin - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Humans; Lipoproteins, HDL - pharmacology; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - physiology; Umbilical Veins; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0021-9150

Monocyte adhesion to and transmigration across the endothelium are initiating steps in atherogenesis. Cytokine-induced adhesion molecule expression in human umbilical vein endothelial cells (HUVEC) has been reported to be inhibited by either native HDL or reconstituted discoidal HDL (rHDL). In the present study we investigated these putative anti-atherosclerotic effects of HDL and rHDL in a more physiologically relevant cell type, i.e. human aortic endothelial cells (HAEC). HDL isolated by ultracentrifugation from eleven healthy subjects or rHDL made with apoA-I and either 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine, 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine (PLPC), or 1,2-dimyristoyl-sn-glycero-3-phosphocholine was incubated for 16 h with HAEC prior to stimulation with tumor necrosis factor-alpha (TNFalpha, 100 U/ml). Expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) was measured by cell ELISA and Northern blot analysis. HDL (0.25, 0.5, 1.0 and 2.0 mgprotein/ml) failed to significantly inhibit TNFalpha-induced mRNA and protein expression of all three adhesion molecules. Furthermore, of the three rHDL preparations (16 micromol/l apoA-I) only that containing the polyunsaturated PLPC significantly reduced TNFalpha-induced VCAM-1 expression (by 29.9+/-9.1%). These data contrast with previously reported results using plasma HDL and HUVEC, and show that human HDL and rHDL, except for PLPC-rHDL, are ineffective inhibitors of TNFalpha-induced adhesion molecule expression in HAEC. The ability of polyunsaturated phospholipids in HDL to affect endothelial activation remains to be further investigated.