scholarly journals Involvement of Heat Shock Factor-1 in Glycated LDL-Induced Upregulation of Plasminogen Activator Inhibitor-1 in Vascular Endothelial Cells

Diabetes ◽  
2007 ◽  
Vol 56 (5) ◽  
pp. 1436-1444 ◽  
Author(s):  
R. Zhao ◽  
G. X. Shen
Keyword(s):  
Endothelial Cells ◽  
Heat Shock ◽  
Plasminogen Activator ◽  
Vascular Endothelial Cells ◽  
Plasminogen Activator Inhibitor ◽  
Heat Shock Factor 1 ◽  
Vascular Endothelial ◽  
Plasminogen Activator Inhibitor 1 ◽  
Glycated Ldl ◽  
Activator Inhibitor

Involvement of NADPH oxidase in oxidized LDL-induced upregulation of heat shock factor-1 and plasminogen activator inhibitor-1 in vascular endothelial cells

2009 ◽  
Vol 297 (1) ◽  
pp. E104-E111 ◽  
Author(s):  
Ruozhi Zhao ◽  
Xiuli Ma ◽  
Xueping Xie ◽  
Garry X. Shen
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Oxidized Ldl ◽  
Plasminogen Activator Inhibitor ◽  
Heat Shock Factor 1 ◽  
Vascular Endothelial ◽  
Plasminogen Activator Inhibitor 1 ◽  
Induced Expression ◽  
Activator Inhibitor ◽  
Pai 1

Plasminogen activator inhibitor-1 (PAI-1) is implicated in thrombogenesis, inflammation, and extracellular matrix remodeling. Previous studies indicated that oxidized low-density lipoprotein (LDL) stimulated the generation of PAI-1 in vascular endothelial cells (EC). The present study demonstrated that LDL oxidized by copper, iron, or 3-morpholinosydnonimine increased the expression of NADPH oxidase (NOX) 2, PAI-1, and heat shock factor-1 (HSF1) in human umbilical vein EC or coronary artery EC compared with LDL or vehicle. Diphenyleneiodonium, a NOX inhibitor, prevented the increases of the expression of HSF1 and PAI-1 in EC induced by oxidized LDLs. Small-interference RNA (siRNA) for p22phox, an essential subunit of NOX, prevented oxidized LDL-induced expression of NOX2, HSF1, and PAI-1 in EC. HSF1 siRNA inhibited oxidized LDL-induced expression of PAI-1 and HSF1, but not NOX2, in EC. The binding of HSF1 to PAI-1 promoter and the activity of PAI-1 promoter in EC were enhanced by oxidized LDL. Butylated hydroxytulene, a potent antioxidant, inhibited oxidized LDL-induced release of hydrogen peroxide (H2O2) and the expression of NOX2, HSF1, and PAI-1 in EC. Treatment with H2O2 increased the abundance of NOX2, HSF1, and PAI-1 in EC. The results of the present study indicate that oxidized LDL-induced expression of NOX may lead to the elevated release of reactive oxygen species, the activation of HSF1, and the enhancement of the transcription of PAI-1 gene in cultured vascular EC.

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