Effects of Intravenous 5-Lipoxygenase Inhibitor Quercetin Therapy on Endothelial Function, Severity of Systemic Inflammation and Oxidative Stress in Acute ST Elevation Myocardial Infarction

Ya.M. Lutai, O.M. Parkhomeko, N.O. Ryzhkova, T.I. Havrylenko, O.I. Irkin, S.M. Kozhukhov, A.O. Stepura, D.O. Bilyi


The objective was to evaluate the antioxidant and anti-inflammatory activity of 5-lipoxygenase inhibitor quercetin, as well as the impact of the drug on endothelial function in patients with acute coronary syndrome (ACS) with ST-segment elevation on the electrocardiogram on the background of modern treatment. The study involved 94 patients who were hospitalized within the first 12 hours of developing symptoms of the disease and received reperfusion therapy by primary angioplasty method. Patients were divided into two groups in a ratio of 2 : 1. In addition to the basic treatment for ACS, 60 patients received 5-lipoxygenase inhibitor quercetin, 34 patients were in the control group. Patients in both groups did not differ in main clinical and anamnestic parameters, characteristics of myocardial infarction and basic treatment. Results of tests with flow-dependent vasodilation (FDV) on the 1st day in both groups did not differ (p = 0.654). During hospital period, we marked a significant increase in brachial artery diameter in FDV in corvitin group (6.45 ± 1.02 % on the 1st day against 9.96 ± 0.94 % on the 7th day, respectively, p = 0.004) in the absence of changes in the control group (p = 0.324). Quercetin therapy had not a significant impact on the dynamics of von Willebrand factor, soluble E-selectin, soluble CD40 ligand and C-reactive protein levels. We have detected a significant increase in the content of vascular endothelial growth factor on the 7th day in quercetin group (149.3 ± 47.2 pcg/ml on the 1st day versus 396.0 ± 64.7 pg/ml on the 7th day, respectively, p = 0.002) as opposed to the control group (p = 0.373). The level of myeloperoxidase (MPO) in the blood plasma of patients with acute myocardial infarction (AMI) on the 1st day in two selected groups did not differ significantly (p = 0.603). We have revealed a strong inverse correlation (r = –0.46; p = 0.006) between MPO content in the blood plasma and results of FDV on the 1st day, as well as an inverse correlation between the changes in MPO level and FDV changes in the dynamics of hospital period (r = –0.40; p = 0.01). Quercetin therapy led to a significant reduction of MPO in the blood plasma of patients with AMI (611.7 ± 83.3 ng/ml on the 1st day versus 382.4 ± 65.4 ng/ml on the 7th day, p = 0.013), which was not observed in the control group (525.9 ± 122.3 ng/ml on the 1st day versus 437.6 ± 104.8 ng/ml on the 7th day, p = 0.210). According to the results of clinical observation, patients who in addition to basic therapy received quercetin were characterized by a decrease in the manifestations of acute left ventricular failure during the hospital period. Thus, the administration of 5-lipoxygenase inhibitor quercetin to AMI patients with ST-segment elevation has not additional anti-inflammatory effect, but has a positive effect on endothelial function and antioxidant properties (reduction of MPO level), which causes downward trend in hospital-acquired complications on the background of quercetin administration, even under modern treatment for ACS.


Parkhomenko A.N., Kozhukhov S.N., Irkin O.I. et al. Cardioprotective effects of 5-lipoxigenase inhibitor quercetine in thrombolysed patients with acute myocardial infarction // XXII Congress of the European Society of Cardiology. Amsterdam (The Netherlands). — 2000. — Europ. Heart J. — 2000. — Vol. 21. (suppl.). — P. 476.

Пархоменко А.Н., Иркин О.И., Кожухов С.Н. Возможности фармакологической защиты миокарда при синдроме ишемии-реперфузии в эксперименте и клинической практике // Ліки України. — 2002. — № 7–8. — С. 2-11.

Moybenko O., Dosenko V., Parkhomenko O. Endogenous mechanisms of cardioprotection as basis of nosotropic therapy of di­seases of heart. — К.: Naukova dumka, 2008.

Нормативно-директивні документи МОЗ України. Інструкція для медичного застосування препарату Кверцетин // = 8711

Verweij C.L. Biosynthesis of human von Willebrand factor // Haemostasis. — 1988. — Vol. 18. — P. 224-245.

Mannucci P.M. von Willebrand factor: a marker of endothelial damage? // Arterioscler. Thromb. Vasc. Biol. — 1998. — Vol. 18. — P. 1359-1362.

Prentice C.R.M. Platelets and atherosclerosis // Eur. Heart J. — 1999. — Vol. 1, Suppl. A. — P. 3A-7A.

Rodeghiero F., Castaman G. The von Willebrand factor // Res. Clin. Lab. — 1990. — Vol. 20. — P. 143-153.

Varo N., de Lemos J.A., Libby P. et al. Soluble CD40L: Risk Prediction After Acute Coronary Syndromes // Circulation. — 2003. — Vol. 108. — P. 1049-1052.

Tischer E., Mitchell R., Hartman T. et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing // J. Biol. Chem. — 1991. — Vol. 266(18). — P. 11947-54.

Tsao K.C., Chang P.Y., Li C.C. et al. Development of a microplate ELISA for circulating E-selectin: assay characterization, comparison with a commercial kit, wand establishment of normal reference values // J. Clin. Lab. Anal. — 2003. — Vol. 17(3). — P. 97-101.

Chang P.Y., Wu T.L., Hung C.C. et al. Development of an ELISA for myeloperoxidase on microplate: normal reference values and effect of temperature on specimen preparation // Clin. Chim. Acta. — 2006. — Vol. 373(1–2). — P. 158-63.

Thijssen D.H., Black M.A., Pyke K.E. et al. Assessment of flow — mediated dilation in humans: a methodological and physio­logical guideline // American Journal of Physiology. — 2011. — Vol. 300. — P. 2-12.

Celermajer D.S., Sorensen K.E., Gooch V.M. et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis // Lancet. — 1992. — Vol. 340. — P. 1111-1115.

Killip T., Kimbal J.T. Triatment of miocardial infarction in a coronary care unit a two year experientse with 250 patients // Am. J. Cardiol. — 1967. — Vol. 20. — 457-464.

StatSoft, Inc. (2004). Statistica (data analysis software system), version 7.

Heeschen C., Dimmeler S., Hamm C.W. et al. Prognostic significance of angiogenic growth factor serum levels in patients with acute coronary syndromes // Circulation. — 2003. — Vol. 107. — P. 524-530.

Zhao T., Zhao W., Chen Y. et al. Vascular endothelial growth factor (VEGF)-A: role on cardiac angiogenesis following myocardial infarction // Microvasc. Res. — 2010. — Vol. 80(2). — P. 188-94.

Miyagi Y., Chiu L.L., Cimini M. et al. Biodegradable collagen patch with covalently immobilized VEGF for myocardial repair // Biomaterials. — 2011. — № 32. — Р. 1280-1290.

Yang Y., Shi C., Hou X. et al. Modified VEGF targets the ­ischemic myocardium and promotes functional recovery after myocardial infarction // J. Control. Release. — 2015. — Vol. 213. —

P. 27-35.

Henn V., Slupsky J.R., Gräfe M. et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells // Nature. — 1998. — Vol. 5; 391(6667). — P. 591-594.

Inwald D.P., McDowall A., Peters M.J. et al. CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation // Circ. Res. — 2003. — Vol. 16; 92. — P. 1041-1048.

Henn V., Slupsky J.R., Gräfe M. et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells // Nature. — 1998. — Vol. 5; 391(6667). — P. 591-594.

Талаева, Т.В. Механизмы взаимодействия клеток крови и сосудистой стенки в реализации воспалительного и иммунного ответов / Т.В. Талаева // Український ревматологічний журнал. — 2001. — № 3–4 (5–6). — С. 45-52.

Alamanda V. et al. Nicotine-mediated induction of E-selectin in aortic endothelial cells requires Src kinase and E2F1 transcriptional activity // Biochem. Biophys. Res. Commun. — 2012. — Vol. 418, № 1. — Р. 56-61.

Klebanoff S. Myeloperoxidase: Friend and foe // J. Leuc. Biol. — 2005. — Vol. 77(5). — P. 598-625.

Peluso I., Morabito G., Urban L., Ioannone F., Serafini M. Oxidative stress in atherosclerosis development: the central role of LDL and oxidative burst // Endocr. Metab. Immune Disord. Drug. Targets. — 2012. — Vol. 12(4). — P. 351-60.

Ruleva N., Zvyaginceva M., Dugin S. Myeloperoxidase: biological functions and clinical value // Modern scientific technologies. — 2007. — Vol. 8. — P. 11-14. [Russian]

Alipour A., Ribalta J., Njo T., Janssen H., Birnie E., van Miltenburg A., Elte J., Castro C. Trans-vessel gradient of myeloperoxidase in coronary artery disease // Eur. J. Clin. Invest. — 2013. — Vol. 43(9). — P. 920-5.

Patterson E., Fraser D., Capretta A., Potter R., Cepinskas G. Carbon monoxide-releasing molecule 3 inhibits myeloperoxidase and protects against MPO-induced vascular endothelial cell activation/dysfunction // Free Radic. Biol. Med. — 2014. — Vol. 26 (70C). — P. 167-73.

Eiserich J.P.1, Baldus S., Brennan M.L. et al. Myeloperoxidase, a leukocyte-derived vascular NO oxidase // Science. — 2002 Jun 28. — Vol. 296(5577). — P. 2391-4.

Kolarova H., Klinke A., Kremserova S., Adam M., Pekarova M., Baldus S., Eiserich J., Kubala L. Myeloperoxidase induces the priming of platelets // Free Radic. Biol. Med. — 2013 Aug. — Vol. 61. — P. 357-69.

Graner M., Tikkanen E., Rimpila O., Tikkanen H., Ripatti S., Lokki M., Niemen M., Taskinen M., Sinisalo J. Diagnostic efficacy of myeloperoxidase to identify acute coronary syndrome in subjects with chest pain // Ann. Med. — 2013 Jun. — Vol. 45(4). — P. 322-7.

Ryzhkova N., Gavrilenko T., Parkhomenko O., Kozhukhov S. Metabolіc activity of neutrocytes and the ways of it are possible correction at of patients from by the acute coronary syndrom // Fіzіol. J. — 2011. — Vol. 57(2). — P. 35-42. [Ukrainian]

Copyright (c) 2016 EMERGENCY MEDICINE

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.


© Publishing House Zaslavsky, 1997-2018


   Seo анализ сайта