Transferable lipids in oxidized low-density lipoprotein stimulate plasminogen activator inhibitor-1 and inhibit tissue-type plasminogen activator release from endothelial cells.
Decreased fibrinolytic activity has been reported in atherosclerotic cardiovascular diseases. To determine whether oxidized low-density lipoprotein (Ox-LDL), which accumulates in atherosclerotic arteries, modulates the endothelial fibrinolytic system, cultures of human umbilical vein endothelial cells were incubated with low-density lipoproteins or lipids, and levels of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) antigens in the conditioned medium were measured by enzyme-linked immunosorbent assay. Ox-LDL (30 micrograms protein/mL) and its extracted lipid (50 micrograms cholesterol/mL) stimulated PAI-1 release by 42 +/- 3% and 29 +/- 3% of control cultures, respectively, whereas Ox-LDL and its lipid inhibited t-PA release by 42 +/- 4% and 53 +/- 3% of control cultures, respectively. Native LDL and its lipid were inactive on their release. Ox-LDL depleted of hydrophilic lipids, which was prepared by the incubation with defatted albumin (an acceptor for hydrophilic lipids), lost both the stimulatory action on PAI-1 and the inhibitory action on t-PA. The extracted lipid from the incubated albumin, which has been found to accept the hydrophilic lipids from Ox-LDL, gained the stimulatory action on PAI-1 and the inhibitory action on t-PA. Ox-LDL depleted of lysophosphatidylcholine (LPC), which was prepared by the incubation with phospholipase B, lost the stimulatory effect on PAI-1, whereas the inhibitory effect on t-PA remained present in the Ox-LDL depleted of LPC. The incubation with synthetic palmitoyl LPC (10 microM) stimulated PAI-1 release by 85 +/- 7% of control.(ABSTRACT TRUNCATED AT 250 WORDS)
Kugiyama
K
K
Division of Cardiology, Kumamoto University School of Medicine, Japan.
Sakamoto
T
T
Misumi
I
I
Sugiyama
S
S
Ohgushi
M
M
Ogawa
H
H
Horiguchi
M
M
Yasue
H
H
D002470:Cell Survival; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D010084:Oxidation-Reduction; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D014176:Protein Biosynthesis; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000378:metabolism
D008055:Lipids; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator