LIPOLYZED HYPERTRIGLYCERIDEMIC SERUM AND TRIGLYCERIDE-RICH LIPOPROTEIN CAUSE LIPID-ACCUMULATION IN AND ARE CYTOTOXIC TO CULTURED HUMAN ENDOTHELIAL-CELLS - HIGH-DENSITY LIPOPROTEINS INHIBIT THIS CYTOTOXICITY

The cytotoxic effect of hypertriglyceridemic (HTG) serum and triglyceride-rich lipoprotein (TG-rich lipoprotein) lipolyzed in vitro by purified lipoprotein lipase on cultured human umbilical vein endothelial cells (HUVECs) was studied. When confluent cultures of HUVECs (8.4 × 104/cm2 ) were incubated in the presence of control (non-lipolyzed HTG serum) or lipolyzed HTG serum or TG-rich lipoprotein, the lipolyzed HTG serum or TG-rich lipoprotein was cytotoxic to the HUVECs as indicated by their detachment from the culture dish; the lipolyzed serum at 10% of the culture medium or lipolyzed TG-rich lipoprotein at 75 μg cholesterol/ml caused the detachment of all (100%) of the cells from the culture dish after a 24 h incubation. Control (non-lipolyzed) HTG serum or non-lipolyzed TG-rich lipoprotein at the same or higher concentration was not cytotoxic to the cells. The HUVECs incubated for 48 h with low (sublethal) doses of lipolyzed TG-rich lipoprotein (10-50 μg cholesterol/ml) contained massive lipid inclusions; no lipid inclusions were seen within the cells when the culture medium contained control non-lipolyzed TG-rich lipoproteins. Finally, when high density lipoprotein (HDL) was added to the culture medium at the same concentration as the cytotoxic lipolyzed TG-rich lipoprotein (75 μg cholesterol/ml), the cytotoxic effect of the lipolyzed TG-rich lipoprotein was inhibited. These data suggest that the interaction of endothelial cells with lipolytic remnants of TG-rich lipoprotein may play a role in the pathogenesis of atherosclerosis and that HDL may play an important role in inhibition of the endothelial cell injury produced by the lipolytic remnants of TG-rich lipoprotein. © 1990.