Lipoproteins inhibit the secretion of tissue plasminogen activator from human endothelial cells.
We studied the effect of lipoprotein(a) [Lp(a)], low-density lipoprotein (LDL), and high-density lipoprotein (HDL) on tissue plasminogen activator (TPA) secretion from human endothelial cells. At 1 mumol/L, Lp(a) inhibited constitutive TPA secretion by 50% and phorbol myristate acetate- and histamine-enhanced TPA secretion by 40%. LDL and HDL also depressed TPA secretion by 45% and 35% (constitutive) and 40% to 60% (stimulated). TPA mRNA levels were also examined and found to change in parallel with antigen secretion. In contrast to TPA, plasminogen activator inhibitor type-1 secretion and mRNA levels were not affected by any of the three lipoproteins. These results suggest that the interaction of lipoproteins with certain cell-surface binding sites may interfere with the proper production and/or secretion of TPA.
Levin
E G
EG
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037.
Miles
L A
LA
Fless
G M
GM
Scanu
A M
AM
Baynham
P
P
Curtiss
L K
LK
Plow
E F
EF
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D017270:Lipoprotein(a) / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D017270:Lipoprotein(a); D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D010959:Tissue Plasminogen Activator