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 x 10(4)/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 micrograms 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 micrograms 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 micrograms 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.
Speidel
M T
MT
Division of Cardiovascular Disease, University of Alabama, Birmingham 35294.
Booyse
F M
FM
Abrams
A
A
Moore
M A
MA
Chung
B H
BH
D001391:Azo Compounds; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism / Q000633:toxicity; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000378:metabolism; D008074:Lipoproteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000633:toxicity*; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008854:Microscopy, Electron; D014280:Triglycerides / Q000378:metabolism*
D001391:Azo Compounds; D004396:Coloring Agents; D008054:Lipid Peroxides; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D014280:Triglycerides; D007770:L-Lactate Dehydrogenase; D008071:Lipoprotein Lipase; C011049:oil red O