ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 23 of 68
Up
JMBS 2021, 6(5): 163–168
https://doi.org/10.26693/jmbs06.05.163
Clinical Medicine

Impact of Reperfusion Therapy on the Levels of Endothelial Nitric Oxide Synthase in Patients with Acute Myocardial Infarction and Type 2 Diabetes Mellitus

Zaikina Т. S., Minukhina D. V., Rynchak P. I., Tytova G. Yu., Zolotaikina V. I.
Abstract

The purpose of the study was to investigate the effect of reperfusion therapy on the levels of endothelial nitric oxide synthase in patients with acute myocardial infarction and concomitant type 2 diabetes mellitus. Materials and methods. The study involved patients with acute myocardial infarction, who were divided into groups depending on the presence of type 2 diabetes mellitus and the therapy performed for them: group 1 – 58 patients with acute myocardial infarction and diabetes mellitus who underwent percutaneous coronary intervention; group 2 – 15 patients with acute myocardial infarction and diabetes mellitus who underwent exclusively conservative treatment; group 3 – 40 patients with acute myocardial infarction without diabetes who underwent percutaneous coronary intervention; group 4 – 17 patients with acute myocardial infarction without diabetes, who underwent exclusively conservative treatment. Results and discussion. According to the obtained results, in patients with concomitant type 2 diabetes mellitus, significantly lower levels of endothelial nitric oxide synthase were revealed, compared with patients without disturbances in carbohydrate metabolism, which indicates deeper impairments of endothelial function against the background of hyperglycemia and insulin resistance. Analysis of the effect of reperfusion therapy showed a statistically significant increase in the level of endothelial nitric oxide synthase both in the group of patients with concomitant disorders of carbohydrate metabolism and without them, which indicates an improvement in the processes of endothelium-dependent dilation, regardless of the presence or absence of type 2 diabetes mellitus. The obtained results testify to the positive effect of percutaneous coronary intervention at the level of eNOS, which, in our opinion, will help to improve the vasodilating properties of vascular endothelium and prevent a complicated course of acute myocardial infarction. Conclusion. The patients with acute myocardial infarction and concomitant type 2 diabetes mellitus have significantly lower levels of endothelial nitric oxide synthase levels than patients without type 2 diabetes mellitus that indicates deep violations of endothelial function against background of metabolic changes associated with insulin resistance and hyperglycemia. Reperfusion therapy accelerates its restoration regardless of the presence or absence of type 2 diabetes mellitus

Keywords: acute myocardial infarction, type 2 diabetes mellitus, endothelial nitric oxide synthase, reperfusion therapy

Full text: PDF (Ukr) 276K

References
  1. Assmann TS, Brondani LA, Bouças AP, Rheinheimer J, de Souza BM, Canani LH, et al. Nitric oxide levels in patients with diabetes mellitus: a systematic review and meta-analysis. Nitric Oxide. 2016; 61: https://www.ncbi.nlm.nih.gov/pubmed/27677584. 1-9. https://doi.org/10.1016/j.niox.2016.09.009
  2. Picard F, Adjedj J, Varenne O. Diabetes Mellitus, a prothrombotic disease. Ann Cardiol Angeiol. 2017; 66(6): 385-2. https://www.ncbi.nlm.nih.gov/pubmed/29106832. https://doi.org/10.1016/j.ancard.2017.10.011
  3. Beckman JA, Paneni F, Cosentino F, Creager MA. Diabetes and vascular disease: pathophysiology, clinical consequences and medical therapy: part II. Eur Heart J. 2013; 34(31): 2444-2452. https://www.ncbi.nlm.nih.gov/pubmed/23625211. https://doi.org/10.1093/eurheartj/eht142
  4. Tousoulis D, Simopoulou C, Papageorgiou N, Oikonomou E, Hatzis G, Siasos G, et al. Endothelial dysfunction in conduit arteries and in microcirculation. Novel therapeutic approaches. Pharmacol Ther. 2014 Dec; 144(3): 253-67. https://www.ncbi.nlm.nih.gov/pubmed/24928320. https://doi.org/10.1016/j.pharmthera.2014.06.003
  5. Bredt DS, Snyder SH. Nitric oxide: a physiologic messenger molecule. Ann Rev Biochem. 1994; 63: 175-195. https://www.ncbi.nlm.nih.gov/pubmed/7526779. https://doi.org/10.1146/annurev.bi.63.070194.001135
  6. Maruhashi T, Higashi Y. Pathophysiological association between diabetes mellitus and endothelial dysfunction. Antioxidants. 2021; 10(8): 1306. https://www.ncbi.nlm.nih.gov/pubmed/34439553. https://www.ncbi.nlm.nih.gov/pmc/articles/8389282. https://doi.org/10.3390/antiox10081306
  7. Bhagat K. Endothelial function and myocardial infarction. Cardiovasc Res. 1998; 39(2): 312-317. https://doi.org/10.1016/S0008-6363(98)00138-2
  8. Zaikina ТS. Prediction model of hospital mortality among patients with acute myocardial infarction and concomitant type 2 diabetes mellitus. Visnyk problem biologiyi i medytsyny. 2016; 1(126): 167-170.
  9. Obata J, Horikoshi T, Nakamura T. Sustained endothelial dysfunction in the infarct-related coronary artery is associated with left ventricular adverse remodeling in survivors of ST-segment elevation myocardial infarction. J Cardiol. 2020; 75: 261-269. https://www.ncbi.nlm.nih.gov/pubmed/31447080. https://doi.org/10.1016/j.jjcc.2019.08.001
  10. Sharma A, Sellers S, Stefanovic N. Direct endothelial nitric oxide synthase activation provides atheroprotection in diabetes-accelerated atherosclerosis. Diabetes. 2015; 64(11): 3937-3950. https://www.ncbi.nlm.nih.gov/pubmed/26116699. https://doi.org/10.2337/db15-0472
  11. Radziwon-Balicka A, Lesyk G, Back V. Differential eNOS-signalling by platelet subpopulations regulates adhesion and aggregation. Cardiovasc Res. 2017; 113(14): 1719-1731. https://www.ncbi.nlm.nih.gov/pubmed/29016749. https://www.ncbi.nlm.nih.gov/pmc/articles/5852541. https://doi.org/10.1093/cvr/cvx179
  12. Daiber A, Xia N, Steven S. New therapeutic implications of endothelial nitric oxide synthase (eNOS) function/dysfunction in cardiovascular disease. Int J Molecular Sci. 2019; 20(1):187. https://www.ncbi.nlm.nih.gov/pubmed/30621010. https://www.ncbi.nlm.nih.gov/pmc/articles/6337296. https://doi.org/10.3390/ijms20010187
  13. Karbach S, Wenzel P, Waisman A. eNOS uncoupling in cardiovascular diseases-the role of oxidative stress and inflammation. Curr Pharm Des. 2014; 20(22): 3579-3594. https://www.ncbi.nlm.nih.gov/pubmed/24180381. https://doi.org/10.2174/13816128113196660748
  14. Du X, Edelstein D, Dimmeler S. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. J Clin Invest. 2001; 108(9): 1341-1348. https://www.ncbi.nlm.nih.gov/pubmed/11696579. https://www.ncbi.nlm.nih.gov/pmc/articles/209429. https://doi.org/10.1172/JCI11235
  15. Gentile C, Kesteven S, Wu J, Bursill C, Davies M, Feneley M, Figtree G. Endothelial nitric oxide synthase plays a protective role against myocardial infarction. Free Radic Biol Med. 2018; 128(1): s26. https://doi.org/10.1016/j.freeradbiomed.2018.10.018
  16. Fangfang L, Jing Z, Hao Z. Orientin reduces myocardial infarction size via eNOS/NO signaling and thus mitigates adverse cardiac remodeling. Front Pharmacol. 2017; 21. https://www.ncbi.nlm.nih.gov/pubmed/29311930. https://www.ncbi.nlm.nih.gov/pmc/articles/5742593. https://doi.org/10.3389/fphar.2017.00926
  17. Jones S, Greer J, van Haperen R. Endothelial nitric oxide synthase overexpression attenuates congestive heart failure in mice. Proc Natl Acad Sci U S A. 2003; 100 (8): 4891-4896. https://www.ncbi.nlm.nih.gov/pubmed/12676984. https://www.ncbi.nlm.nih.gov/pmc/articles/153651. https://doi.org/10.1073/pnas.0837428100
  18. Kytö V, Prami T, Khanfir H. Usage of PCI and long-term cardiovascular risk in post-myocardial infarction patients: a nationwide registry cohort study from Finland. BMC Cardiovasc Disord. 2019; 19: 123. https://www.ncbi.nlm.nih.gov/pubmed/31117956. https://www.ncbi.nlm.nih.gov/pmc/articles/6532224. https://doi.org/10.1186/s12872-019-1101-8
  19. Belen'kova Y, Karetnikova V, Dyachenko A. Effektivnost chreskozhnoho koronarnoho vmeshatelstva u patsientov s infarktom miokarda s podemom sehmenta st na fone narushennoy tolerantnosti k hlyukoze i sakharnoho diabeta [Efficacy of percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction in the presence of impaired glucose tolerance and diabetes mellitus]. Kardiologiya. 2014; 11: 4-10. [Russian]. https://www.ncbi.nlm.nih.gov/pubmed/25902652. https://doi.org/10.18565/cardio.2014.11.4-10
  20. Petyunina O, Kopytsya M, Babichev D, Berezin A. Short-term clinical outcomes in patients with acute myocardial infarction after successful percutaneous coronary revascularization: the role of promoter polymorphism of the endothelial nitric oxide synthase gene. Biomed Res Ther. 2019; 6(5): 3166-3179. https://doi.org/10.15419/bmrat.v6i5.543
  21. Shishkina E, Khlynova O, Tuev A, Krivtsov A. Polimorfizm T786C hena endotelialnoy sintazy oksida azota kak faktor riska povtornoho infarkta miokarda u bolnykh molodoho i sredneho vozrasta [T786C eNOS polymorphism as risk factor for recurrent myocardial infarction in young and middleaged patients]. Med alphabet. 2020; (28): 17-21. [Russian]. https://doi.org/10.33667/2078-5631-2020-28-17-21