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

Watt, J., Ewart, M.-A., Greig, F.H., Oldroyd, K.G., Wadsworth, R.M. and Kennedy, S. (2012) The effect of reactive oxygen species on whole blood aggregation and the enothelial cell-platelet interaction in patients with coronary heart disease. Thrombosis Research, 130(2), pp. 210-215. (doi: 10.1016/j.thromres.2012.03.024)

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, 100μM xanthine and 100mU/ml xanthine oxidase inhibited WBA in response to 3μg/ml collagen by 28.9% (95% CI 15.9%-41.8%, p<0.001) and in response to 5μM 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 3μg/ml collagen by 31.2% (95% CI 12.2%-50.2%, p<0.05) and in response to 5μM 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kennedy, Professor Simon and Oldroyd, Dr Keith and Ewart, Dr Marie-Ann and Wadsworth, Prof Roger
• Authors: Watt, J., Ewart, M.-A., Greig, F.H., Oldroyd, K.G., Wadsworth, R.M., and Kennedy, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Thrombosis Research
• ISSN: 0049-3848
• ISSN (Online): 1879-2472
• Published Online: 20 April 2012