Effects of oxidized and glycated low-density lipoproteins on transcription and secretion of plasminogen activator inhibitor-1 in vascular endothelial cells.
Cardiovasc Pathol
; 15(1): 3-10, 2006.
Article
em En
| MEDLINE
| ID: mdl-16414450
ABSTRACT
Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of fibrinolysis. Elevated levels of PAI-1 were frequently detected in patients with coronary artery disease (CAD) or diabetes. Low-density lipoprotein (LDL) is a classical risk factor of CAD. Oxidation and glycation increase the atherogenecity of LDL. Previous studies demonstrated that oxidized LDL (oxLDL) or glycated LDL (gly-LDL) increased the release of PAI-1 from endothelial cells (ECs). The present study examined the effects of oxLDL and gly-LDL on the transcription, expression, secretion, and subcellular distribution of PAI-1 in cultured human ECs. Treatment with LDL significantly increased the promoter activity, mRNA level, and the release of PAI-1 from ECs by two- to threefold compared to controls. Oxidation or glycation significantly enhanced the effects of LDL on PAI-1 production in ECs compared to LDL (four- to fivefold vs. controls). No significant differences were detected between the effects of oxLDL and gly-LDL. Abundant PAI-1 antigens were detected in the perinuclear region of ECs and overlapped with giantin, a marker of Golgi apparatus. Treatment with brefeldin A disturbed the stack structure of Golgi apparatus and almost completely inhibited the release of PAI-1 from ECs induced by the lipoproteins and at basal conditions. The results suggest that oxidation and glycation enhanced the effects of LDL on the production of PAI-1 in ECs through increasing the transcription of PAI-1. Intact Golgi apparatus is required for PAI-1 generation from ECs induced by LDL or its modified forms.
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Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Inibidor 1 de Ativador de Plasminogênio
/
Células Endoteliais
/
Lipoproteínas LDL
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cardiovasc Pathol
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
PATOLOGIA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Canadá