Platelet metabolic features in patients with stable angina regarding aspirin resistant

Authors: I.Y. Grinshteyn 1, A.A. Savchenko 1,2, 2, Y.I. Grinshteyn 1, E.A. Savchenko 1

Company: 1 Prof. V.F. Voyno-Yasenetskiy Krasnoyarsk State Medical University of Ministry of Health of the Russian Federation; ulitsa Partizana Zheleznyaka, 1, Krasnoyarsk, 660022, Russian Federation; 2 Institute of Medical Problems of the North, Siberian Division, Russian Academy of Medical Sciences; ulitsa Partizana Zheleznyaka, 3G, Krasnoyarsk, Russian Federation


For citation: Grinshteyn I.Yu., Savchenko A.A., Grinshteyn Yu.I., Savchenko E.A. Platelet metabolic features in patients with stable angina regarding aspirin resistant. Creative Cardiology. 2014; 1: 15-24

Keywords: stenocardia platelets nicotinamid adenine dinucleotide- and nicotinamide adenine dinucleotide phosphate-dependent dehydrogenases aspirin resistance.

Full text:  

 

Abstract

Objective. To determine of the nicotinamid adenine dinucleotide- and nicotinamide adenine dinucleotide phosphate-dependent (respectively, NAD-and NADP-dependent) dehydrogenases activity in platelets of aspirin-sensitive (ASP) and aspirin-resistant (ARP) patients with II–IV functional classes (FC) stenocardia. Material and methods. In 102 male patients with FC II–IV stenocardia aged 38–73 years were determined hemostasis on aspirin therapy at a dose of 75–150 mg/day. Platelet function was evaluated by optical aggregometry in determination of spontaneous and induced by adenosine diphosphate (ADP) platelet aggregation. Depending on the suppression of platelet aggregation, all patients were divided into two groups: sensitive (n=48) and resistant (n=54) for aspirin. The groups were matched on the number of patients with different functional classes. NAD- and NADP-dependent dehydrogenases activity in blood platelets was determined by biochemiluminescence analyzer BCL 3606M (SCTB "Nauka", Krasnoyarsk). Studied the activity of the following enzymes: glucose-6- phosphate dehydrogenase (Glu-6-pDH), glycerol-3-phosphate dehydrogenase (Gly-3-pDH), malic enzyme (ME), NAD and NADH-dependent reaction of lactate dehydrogenase (LDH and NADH-LDH), NAD and NADH-dependent reaction of malate dehydrogenase (MDH and NADH-MDH), NAD-and NADP-dependent glutamate dehydrogenase (NAD-GluDH and NADP-GluDH), NAD-and NADP-dependent isocitrate dehydrogenases (NAD-ICDH and NADP-ICDH) and glutathione reductase (GluRed). Results. In the study of the NAD-and NADP-dependent dehydrogenases activity platelets depending on stenocardia and sensitivity to aspirin found that III FC ASP relative to control levels had increased activity of NADH-LDH, MDH and NADH NADH-GDH. Activity of GluRed in IV FC ARP increased relative control parameters. Found an increase of the NADH-GDH activity in ASP of IV FC stenocardia relative to a reference range. Conclusion. In patients with stenocardia of III–IV FC according to the sensitivity to aspirin revealed significant differences in the metabolism of platelets. The most pronounced disorders of NAD(P)-dependent dehydrogenases activity in platelets found in IV FC ARP. It is shown that disturbances in the platelet metabolism increase as functional class of stenocardia and are most pronounced in patients resistant to aspirin.

References

1. Cawaz M., Langer H., May A.E. Platelet inflammation and atherosclerosis. J. Clin. Invest. 2005; 115: 3378–84. 2. Воробьева И.И., Рыжкова Е.В., Васильева Е.Ю., Шпектор А.В. Влияние системного воспаления на эффект антиагрегантной терапии у больных с острым коронарным синдромом. Креативная кардиология. 2012; 1: 5–14. 3. Гринштейн Ю.И., Савченко А.А., Гринштейн И.Ю., Савченко Е.А. Особенности гемостаза, метаболической активности тромбоцитов и частота резистентности к аспирину у больных с хронической сердечной недостаточностью после аортокоронарного шунтирования. Кардиология. 2008; 6: 51–6. 4. Пак Н.Л., Голухова Е.З., Самсонова Н.Н. и др. Состояние системы гемостаза у больных ишемической болезнью сердца после операции реваскуляризации миокарда, выполненной в условиях искусственного кровообращения и на работающем сердце. Креативная кардиология. 2011; 2: 60–70. 5. Bonello L., Tantry U.S., Marcucci R. et al. Working Group on High On-Treatment Platelet Reactivity. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J. Am. Coll. Cardiol. 2010; 56: 919–33. 6. Krasopoulos G., Brister S.J., Beattie W.S. et al. Aspirin «resistance» and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ. 2008; 336 (7637): 195–8. 7. Савченко Е.А., Савченко А.А., Герасимчук А.Н., Грищенко Д.А. Оценка метаболического статуса тромбоцитов в норме и при ишемической болезни сердца. Клиническая лабораторная диагностика. 2006; 5: 33–6. 8. Ho H.Y., Cheng M.L., Chiu D.T. Glucose-6-phosphate dehydrogenase-from oxidative stress to cellular functions and degenerative diseases. Redox Rep. 2007; 12; 3: 109–18. 9. Stanton R.C. Glucose-6-phosphate dehydrogenase, NADPH, and cell survival. IUBMB Life. 2012; 64; 5: 362–9. 10. Северин Е.С. (ред.) Биохимия. М.: ГЭОТАР-Медиа; 2004. 11. De la Roche M., Tessier S.N., Storey K.B. Structural and functional properties of glycerol-3-phosphate dehydrogenase from a mammalian hibernator. Protein J. 2012; 31 (2): 109–19. 12. Guo Z.P., Zhang L., Ding Z.Y. et al. Improving ethanol productivity by modification of glycolytic redox factor generation in glycerol-3-phosphate dehydrogenase mutants of an industrial ethanol yeast. J. Ind. Microbiol. Biotechnol. 2011; 38 (8): 935–43. 13. Al-Dwairi A., Pabona J.M., Simmen R.C., Simmen F.A. Cytosolic malic enzyme 1 (ME1) mediates high fat diet-induced adiposity, endocrine profile, and gastrointestinal tract proliferation-associated biomarkers in male mice. PLoS One. 2012 (7); 10: 46716. 14. Murugan S., Hung H.C. Biophysical characterization of the dimer and tetramer interface interactions of the human cytosolic malic enzyme. PLoS One. 2012; 7 (12): 50143. 15. Hayashi T., Tanaka S., Hori Y. et al. Role of mitochondria in the maintenance of platelet function during in vitro storage. Transfus. Med. 2011; 21 (3): 166–74. 16. Misztal T., Przeslaw K., Rusak T., Tomasiak M. Peroxynitrite – altered platelet mitochondria – a new link between inflammation and hemostasis. Thromb. Res. 2013; 131 (1): 17–25.

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery