Increased synthesis of plasminogen activator inhibitor-1 by cultured human endothelial cells exposed to native and modified LDLs: An LDL receptor-independent phenomenon

E. Tremoli, M. Camera, P. Maderna, L. Sironi, L. Prati, S. Colli, F. Piovella, F. Bernini, A. Corsini, L. Mussoni

Research output: Contribution to journalArticle

Abstract

The effects of native and acetylated low density lipoproteins (LDLs and acetyl-LDLs, respectively) on the release of plasminogen activator inhibitor type 1 (PAI-1) by cultured human umbilical vein endothelial cells (ECs) were evaluated. LDL and acetyl-LDL incubated with ECs for 16-18 hours increased the PAI-1 antigen levels in conditioned medium. At a concentration of 100 μg/mL, LDL and acetyl-LDL increased PAI-1 by 10.8 and 12.0 ng/mL, respectively (p35S]methionine-labeIed ECs was not affected, and studies with cycloheximide showed that the effect of LDL and acetyl-LDL on PAI-1 release was due to de novo protein synthesis. Experiments using the C7 monoclonal antibody against the LDL receptor and binding-defective LDL indicated that the effect of LDL on the synthesis of PAI-1 was not dependent on the interaction of the LDLs with their specific receptors. Finally, extensive oxidation of LDL prevented and even reversed the effect of LDL on PAI-1 release bv ECs. It is concluded that LDL specifically increases the svnthesis of PAI-1 by ECs with mechanisms that are not receptor mediated.

Original languageEnglish
Pages (from-to)338-346
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume13
Issue number3
Publication statusPublished - 1993

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Keywords

  • Endothelial cells
  • LDL
  • Modified LDL
  • Plasminogen activator inhibitor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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