Remnant lipoproteins induce endothelial plasminogen activator inhibitor-1.
Remnant lipoproteins (RLPs) accumulate in type III hyperlipoproteinemia, a condition associated with significant cardiovascular morbidity. The effect of RLPs on fibrinolysis is unknown. Our aim was to study the effect of RLPs on endothelial expression of plasminogen activator inhibitor-1 (PAI-1). After 24-h culture of human aortic endothelial cells with RLPs at concentrations of 0 (control), 0.038, or 0.076 mg triglyceride/mL, postculture PAI-1 antigen concentrations were: 870 +/- 80, 1963 +/- 183 (P = 0.005), and 3551 +/- 177 ng/mL (P < 0.001), respectively. Furthermore, after 24-h incubation of endothelial cells with RLPs (0 or 0.076 mg triglyceride/mL), PAI-1 activity increased from 0.667 +/- 0.144 to 1.268 +/- 0.198 U/mL, respectively (P = 0.008) and endothelial PAI-1 mRNA increased to 2.7 +/- 0.66 that of control (P = 0.048). In conclusion, RLPs from patients with type III hyperlipoproteinemia induce endothelial cell PAI-1 expression, which may contribute to a prothrombotic state.
Sawka
A M
AM
Division of Endocrinology, Metabolism, and Nutrition, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Singh
R J
RJ
Hiddinga
H J
HJ
McConnell
J P
JP
Eberhardt
N L
NL
Caplice
N M
NM
O'Brien
T
T
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D006951:Hyperlipoproteinemias / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator