The effect of reactive oxygen species on whole blood aggregation and the endothelial cell-platelet interaction in patients with coronary heart disease

Jonathan Watt, Marie-Ann Ewart, Fiona H Greig, Keith G Oldroyd, Roger M Wadsworth, Simon Kennedy

Research output: Contribution to journalArticle

20 Citations (Scopus)
23 Downloads (Pure)

Abstract

Background
The effect of reactive oxygen species (ROS) on platelet function in coronary heart disease (CHD) is complex and poorly defined. Platelet aggregation studies in healthy volunteers have demonstrated contrasting results when platelets are exposed to ROS. We investigated the effect of ROS on whole blood aggregation (WBA) and the endothelial cell-platelet interaction in patients with CHD.

Methods and Results
ROS generated by xanthine and xanthine oxidase caused a concentration-dependent inhibition of WBA in blood from healthy donors and patients with CHD. In patients with CHD, 100 μM xanthine and 100 mU/ml xanthine oxidase inhibited WBA in response to 3 μg/ml collagen by 28.9% (95% CI 15.9%-41.8%, p < 0.001) and in response to 5 μM ADP by 36.0% (95% CI 9.6%-62.4%, p = 0.005). Using nitrotyrosine expression, platelets isolated from patients with CHD were found to be susceptible to peroxynitrite damage. The addition of 1 × 105 cultured endothelial cells inhibited WBA in response to 3 μg/ml collagen by 31.2% (95% CI 12.2%-50.2%, p < 0.05) and in response to 5 μM ADP by 31.6% (95% CI 2.5-60.7%, p < 0.05). Addition of xanthine and xanthine oxidase did not alter this effect, however pre-treatment of endothelial cells with a nitric oxide synthase inhibitor (L-NAME) partly reversed the inhibition.

Conclusion
ROS inhibit WBA in blood from patients with CHD. Whilst endothelial cells also inhibit WBA, the effect is attenuated by L-NAME, suggesting that nitric oxide is likely to remain an important protective mechanism against thrombosis in CHD.
Original languageEnglish
Pages (from-to)210-215
Number of pages6
JournalThrombosis Research
Volume130
Issue number2
DOIs
Publication statusPublished - Aug 2012

Keywords

  • aged
  • blood platelets
  • cell communication
  • coronary disease
  • endothelial cells
  • endothelium, vascular
  • enzyme inhibitors
  • female
  • hemostasis
  • humans
  • male
  • middle aged
  • NG-nitroarginine methyl ester
  • platelet aggregation
  • reactive oxygen species
  • tyrosine
  • xanthine
  • xanthine oxidase

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