J Korean Med Sci.  2012 Jul;27(7):803-810. 10.3346/jkms.2012.27.7.803.

Impact of Lysophosphatidylcholine on the Plasminogen Activator System in Cultured Vascular Smooth Muscle Cells

• Yoon BK
• Kang YH
• Oh WJ
• Park K
• Lee DY
• Choi D
• Kim DK
• Lee Y
• Rhyu MR

• KMID: 2157928
• DOI: http://doi.org/10.3346/jkms.2012.27.7.803

Abstract

The balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis. PAI-1 expression increases in atherosclerotic arteries and vascular smooth muscle cells (VSMCs) are one of major constituents of atheroma. We investigated the impact of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, on the plasminogen activator system of the rat VSMCs. The lysoPC stimulated the protein and gene expressions of PAI-1 but did not affect the protein expression of t-PA. Fibrin overlay zymography revealed that lysoPC increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA. Vitamin E inhibited the lysoPC-induced PAI-1 expression. Further, lysoPC increased the intracellular reactive oxygen species (ROS) formation. Caffeic acid phenethyl ester, an inhibitor of NF-kappaB, blocked this lysoPC effect. Indeed, lysoPC induced the NF-kappaB-mediated transcriptional activity as measured by luciferase reporter assay. In addition, genistein, an inhibitor of protein-tyrosine kinase (PTK), diminished the lysoPC effect, while 7,12-dimethylbenz[a]anthracene, a stimulator of PTK, stimulated PAI-1 production. In conclusion, lysoPC does not affect t-PA expression but induces PAI-1 expression in the VSMC by mediating NF-kappaB and the genistein-sensitive PTK signaling pathways via oxidative stress. Importantly, lysoPC stimulates the enzyme activity of PAI-1 and suppresses that of t-PA.

Keyword

Lysophosphatidylcholines; NF-kappa B; Oxidative Stress; Plasminogen Activator Inhibitor 1; Protein-Tyrosine Kinase; Muscle, Smooth, Vascular

MeSH Terms

Animals
Benz(a)Anthracenes/pharmacology
Caffeic Acids/pharmacology
Cells, Cultured
Genistein/pharmacology
Lipoproteins, LDL/metabolism
Lysophosphatidylcholines/*pharmacology
Muscle, Smooth, Vascular/cytology/*drug effects/metabolism
NF-kappa B/antagonists & inhibitors/metabolism
Oxidative Stress/drug effects
Phenylethyl Alcohol/analogs & derivatives/pharmacology
Plasminogen Activator Inhibitor 1/agonists/genetics/*metabolism
Protein Kinase Inhibitors/pharmacology
Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species/metabolism
Signal Transduction/drug effects
Tissue Plasminogen Activator/*metabolism
Transcription, Genetic/drug effects
Up-Regulation/drug effects
Vitamin E/pharmacology
Benz(a)Anthracenes
Caffeic Acids
Lipoproteins, LDL
Lysophosphatidylcholines
NF-kappa B
Plasminogen Activator Inhibitor 1
Protein Kinase Inhibitors
Reactive Oxygen Species
Vitamin E
Genistein
Phenylethyl Alcohol
Protein-Tyrosine Kinases
Tissue Plasminogen Activator