Inability of plasma high-density lipoproteins to inhibit cell adhesion molecule expression inhuman coronary artery endothelial cells

High-density lipoproteins (HDL) have several antiatherogenic actions, inclu ding the ability to sequester cellular cholesterol, to protect low-density lipoproteins from oxidation and to inhibit platelet aggregation. An early e vent in atherogenesis is the adhesion and recruitment of blood monocytes, a process mediated by cell adhesion molecules (CAMs), including vascular cel l adhesion molecule-1 (VCAM-1) which is rapidly synthesized by endothelial cells in response to cytokines. It has been reported that HDL limits CAM ex pression in cultured human umbilical vein endothelial cells (HUVECs), imply ing that HDL also protects at an early stage in lesion development. Here, w e have studied HDL suppression of CAM induction in human coronary artery en dothelial cells (HCAECs), a model directly relevant to blood vessels suscep tible to atherosclerosis. Arterial endothelial cells were preincubated with increasing amounts of total HDL, or different subfractions, and then activ ated with the inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha ). Flow cytometric analysis failed to detect any downregulation of VCAM-1 o r E-selectin expression by HDL in this model of vascular endothelium. Moreo ver, we were unable to confirm that HDL could suppress CAM induction in wel l-characterized, low-passage HUVECs, even though positive controls, 17 beta -estradiol or a nitric oxide donor, did cause downregulation and factors s uch as variability in donors and HDL preparation, or culture conditions, we re excluded. We tentatively conclude that, as isolated HDL. did not downreg ulate CAM expression in cultured HCAECs or HUVECs, attenuation of CAM induc tion in arterial endothelium is unlikely to contribute to HDL antiatherogen ic actions in vivo. (C) 2001 Elsevier Science Ireland Ltd. All rights reser ved.