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Tissue plasminogen activator genetic polymorphisms do not influence tissue plasminogen activator release in patients

S D Robinson1, C A Ludlam, N A Boon

  • 1Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. simon.robinson@ed.ac.uk

Journal of Thrombosis and Haemostasis : JTH
|July 14, 2006
PubMed

Insights

Genetic variations in the tissue plasminogen activator (t-PA) gene do not affect acute t-PA release in patients with coronary heart disease (CHD). Smokers showed impaired endothelial function compared to non-smokers.

Area of Science:

  • Cardiovascular Genetics
  • Endothelial Function
  • Thrombosis Research

Background:

  • Coronary heart disease (CHD) involves complex genetic and environmental factors.
  • Tissue plasminogen activator (t-PA) plays a crucial role in fibrinolysis.
  • Endothelial dysfunction is a hallmark of established CHD.

Purpose of the Study:

  • To investigate the association between t-PA gene polymorphisms and acute endogenous t-PA release.
  • To assess the impact of these polymorphisms on endothelial function in CHD patients.
  • To evaluate the influence of smoking on t-PA release and endothelial response.

Main Methods:

  • Studied 96 patients with stable CHD.
  • Measured forearm blood flow and plasma t-PA concentrations after substance P and sodium nitroprusside infusion.
  • Genotyped four specific t-PA gene polymorphisms using polymerase chain reaction.

Main Results:

  • Substance P and sodium nitroprusside induced dose-dependent vasodilation, independent of t-PA gene polymorphisms.
  • No significant differences in basal t-PA levels or release were observed between genotypes.
  • Smokers demonstrated impaired vasodilatation and reduced t-PA release compared to non-smokers.

Conclusions:

  • t-PA gene polymorphisms do not significantly influence acute t-PA release or endothelial function in CHD patients.
  • Genetic variation at the t-PA locus is unlikely to be a major determinant of t-PA release in established CHD.
  • Smoking detrimentally affects endothelial function and t-PA release, reinforcing its role in cardiovascular disease.
Abstract

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