Expression of Plasminogen Activator Inhibitor Type I in Genotyped Human Endothelial Cell Cultures: Genotype-specific Regulation by Insulin

Hernan E. Grenett; Raymond L. Benza; Xin-Nong Li; Michael L. Aikens; John R. Grammer; Stephen L. Brown; Francois M. Booyse

doi:10.1055/s-0037-1614862

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(05): 1504-1509
DOI: 10.1055/s-0037-1614862

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Schattauer GmbH

Expression of Plasminogen Activator Inhibitor Type I in Genotyped Human Endothelial Cell Cultures: Genotype-specific Regulation by Insulin

Hernan E. Grenett

¹From the Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

,

Raymond L. Benza

¹From the Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

,

Xin-Nong Li

¹From the Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

,

Michael L. Aikens

¹From the Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

,

John R. Grammer

¹From the Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

,

Stephen L. Brown

¹From the Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

,

Francois M. Booyse

¹From the Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

› Author Affiliations

Abstract

Summary

Patients with non-insulin-dependent diabetes mellitus frequently have been associated with elevation in plasma levels of PAI-1. Part of the variations in individual plasma PAI-1 levels have been attributed to variations in the PAI-1 gene. In order to determine whether insulin regulates PAI-1 expression in a genotype-specific manner, individual human umbilical vein ECs (HUVECs) were genotyped using a HindIII RFLP and incubated in the absence/presence of insulin. Treatment of 1/1 PAI-1 genotype HUVECs with insulin increased secretion of PAI-1 antigen ~ 1.7 to 2.2-fold and mRNA levels were increased ~ 1.8 to 2.8-fold. Treatment of HUVECs with actinomycin D or puromycin completely abolished the induction of PAI-1 by insulin. The nuclear run-on assays indicated ~3-4 fold increase in PAI-1 transcription rates. These in vitro studies with the 1/1 PAI-1 genotyped cultured HUVECs, suggests that hyperinsulinemia may be expected to increase EC PAI-1 synthesis in those patients with the responsive 1/1 genotype.

Key words

Endothelial cells - PAI-1 - insulin - genotypes - regulation

Full Text

References

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