TY - JOUR
T1 - Remnant lipoproteins induce endothelial plasminogen activator inhibitor-1
AU - Sawka, Anna M.
AU - Singh, Ravinder J.
AU - Hiddinga, H. Jay
AU - McConnell, Joseph P.
AU - Eberhardt, Norman L.
AU - Caplice, Noel M.
AU - O'Brien, Timothy
N1 - Funding Information:
Dr. A. M. Sawka was supported, in part, by a grant from the Endocrine Fellows Foundation. We thank Dr. G. Shen for kindly providing the plasmid containing the cDNA fragment encoding human plasminogen activator inhibitor-1. We also thank Mrs. Sharon Stephan for her expert technical assistance.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Endothelial cells
KW - Fibrinolysis
KW - Plasminogen activator inhibitor-1
KW - Remnant lipoproteins
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U2 - 10.1006/bbrc.2001.5117
DO - 10.1006/bbrc.2001.5117
M3 - Article
C2 - 11437365
AN - SCOPUS:0034794740
SN - 0006-291X
VL - 285
SP - 15
EP - 19
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -