ASSOCIATION OF MMP-9 GENETIC POLYMORPHISM AND ММР-9 CONCENTRATION WITH ECHOCARDIOGRAPHIC PARAMETERS IN UKRAINIAN PATIENTS WITH CORONARY ARTERY DISEASE

Keywords: MMP-9; genetic polymorphism; coronary artery disease; echocardiography

Abstract

Introduction. Cardiovascular diseases are the main cause of reduced life expectancy, workability, and death among the people of Eastern Europe. Matrix metalloproteinase-9 (MMP-9) is known as one of the leading factors involved in the development and progression of atherosclerosis and heart remodeling. The increasing sizes of the heart’s chambers lead to changes in the electrophysiological properties of the myocardium and to the subsequent occurrence of arrhythmias and conduction disorders.

Materials and methods. The study included 25 patients with intact coronary arteries (CA), 40 patients with acute coronary syndrome (ACS) and 63 patients with chronic coronary syndrome (CCS) to investigate the effect of MMP-9 polymorphism and its serum concentration on changes in echocardiographic parameters. Real-time PCR was carried out for genotyping on the rs17567-polymorphic locus and ELISA study was performed to measure the MMP-9 plasma concentration.

Results. Statistically significant differences were found in the thickness of the posterior wall of the heart among carriers of the G-allele and AA-homozygotes for the MMP-9 rs17576-single nucleotide polymorphism but only in patients with ACS. The size of the left ventricle posterior wall can be predicted for carriers of these genotypes.

Conclusions. The study revealed no statistically significant relationship between MMP-9 concentration and echocardiographic parameters in patients with ACS and CCS. However, there were statistically significant differences in the left atrium diameter and thickness of the posterior wall of the left ventricle depending on the genotype for MMP-9 rs17576-single nucleotide polymorphism only in patients with ACS. The size of the posterior wall of the left ventricle can be predicted for carriers of AG and GG genotypes.

Author Biographies

Oksana Pogorielova, Department of Internal Medicine with Center of Respiratory Medicine, Sumy State University, Sumy, Ukraine

Department of Internal Medicine with Center of Respiratory Medicine, Sumy State University (o.s.pogorielova@gmail.com)

Viktoriia Korniienko, Biomedical Research Center, Sumy State University, Sumy, Ukraine

Biomedical Research Center, Sumy State University (vicorn77g@gmail.com)

Yaroslav Chumachenko, Scientific Laboratory of Molecular Genetic Studies, Sumy State University, Sumy, Ukraine

Scientific Laboratory of Molecular Genetic Studies, Sumy State University (yaroslavus.dm@gmail.com)

Olha Obukhova, Department of Physiology and Pathophysiology with Medical Biology Course, Sumy, Ukraine

Department of Physiology and Pathophysiology with Medical Biology Course, Sumy State University (o.obukhova@med.sumdu.edu.ua)

Igor Martsovenko, Municipal Non-Profit Enterprise of Sumy Regional Council «Sumy Regional Cardiological Clinic», Sumy, Ukraine

Municipal Non-Profit Enterprise of Sumy Regional Council «Sumy Regional Cardiological Clinic» (igmar777@i.ua)

Andrii Grek, Department of Internal Medicine with Center of Respiratory Medicine, Sumy State University, Sumy, Ukraine

Department of Internal Medicine with Center of Respiratory Medicine, Sumy State University (kubuldg@gmail.com)

Liudmila Prystupa, Department of Internal Medicine with Center of Respiratory Medicine, Sumy State University, Sumy, Ukraine

Department of Internal Medicine with Center of Respiratory Medicine, Sumy State University (therapiasumdu@gmail.com)

Viktoriia Harbuzova, Scientific Laboratory of Molecular Genetic Studies, Sumy State University, Sumy, Ukraine

Department of Physiology and Pathophysiology with Medical Biology Course, Sumy State University (v.garbuzova@med.sumdu.edu.ua)

References

1. Okrainec K, Banerjee DK, Eisenberg MJ. Coronary artery disease in the developing world. Am Heart J. 2004;148(1):7-15. doi: https://doi.org/10.1016/j.ahj.2003.11.027
2. Sharma K, Gulati M. Coronary artery disease in women: A 2013 update. Glob Heart. 2013;8(2):105-112. doi: https://doi.org/10.1016/j.gheart.2013.02.001
3. Hassanzadeh-Makoui R, Razi B, Aslani S, Imani D, Tabaee SS. The association between Matrix Metallo-proteinases-9 (MMP-9) gene family polymorphisms and risk of Coronary Artery Disease (CAD): A systematic review and meta-analysis. BMC Cardiovasc Disord. 2020;20(1):1-15. doi: https://doi.org/10.1186/s12872-020-01510-4
4. Wang X, Khalil RA. Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease. In: Advances in Pharmacology. Vol 81. Academic Press Inc.; 2018:241-330. doi: https://doi.org/10.1016/bs.apha.2017.08.002
5. Brown BA, Williams H, George SJ. Evidence for the Involvement of Matrix-Degrading Metalloproteinases (MMPs) in Atherosclerosis. In: Progress in Molecular Biology and Translational Science. Vol 147. Elsevier B.V.; 2017:197-237. doi: https://doi.org/10.1016/bs.pmbts.2017.01.004
6. Myasoedova VA, Chistiakov DA, Grechko AV, Orekhov AN. Matrix metalloproteinases in pro-atherosclerotic arterial remodeling. J Mol Cell Cardiol. 2018;123:159-167. doi: https://doi.org/10.1016/j.yjmcc.2018.08.026
7. Bäck M, Ketelhuth DFJ, Agewall S. Matrix Metalloproteinases in Atherothrombosis. Prog Cardiovasc Dis. 2010;52(5):410-428. doi: https://doi.org/10.1016/j.pcad.2009.12.002
8. Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994;94(6):2493-2503. doi: https://doi.org/10.1172/JCI117619
9. Gai X, Lan X, Luo Z, et al. Association of MMP-9 gene polymorphisms with atrial fibrillation in hypertensive heart disease patients. Clin Chim Acta. 2009;408(1-2):105-109. doi: https://doi.org/10.1016/j.cca.2009.07.020
10. Fiotti N, Calvagna C, Sgorlon G, et al. Multiple sites of vascular dilation or aneurysmal disease and matrix metalloproteinase genetic variants in patients with abdominal aortic aneurysm. J Vasc Surg. 2018;67(6):1727-1735. doi: https://doi.org/10.1016/j.jvs.2017.09.047
11. Mishra A, Srivastava A, Mittal T, Garg N, Mittal B. Association of matrix metalloproteinases (MMP2, MMP7 and MMP9) genetic variants with left ventricular dysfunction in coronary artery disease patients. Clin Chim Acta. 2012;413(19-20):1668-1674. doi: https://doi.org/10.1016/j.cca.2012.05.012
12. Wang L, Ma YT, Xie X, et al. Interaction between MMP-9 gene polymorphisms and smoking in relation to myocardial infarction in a uighur population. Clin Appl Thromb. 2012;18(1):72-78. doi: https://doi.org/10.1177/1076029611412365
13. Zhi H, Wang H, Ren L, et al. Functional polymorphisms of matrix metallopeptidase-9 and risk of coronary artery disease in a Chinese population. Mol Biol Rep. 2010;37(1):13-20. doi: https://doi.org/10.1007/s11033-009-9482-x
14. Wu N, Lu X, Hua Y, et al. Haplotype analysis of the stromelysin-1 (MMP3) and gelatinase B (MMP9) genes in relation to coronary heart disease. Ann Hum Genet. 2009;73(4):404-410. doi: https://doi.org/10.1111/j.1469-1809.2009.00522.x
15. Nanni S, Melandri G, Hanemaaijer R, et al. Matrix metalloproteinases in premature coronary atherosclerosis: influence of inhibitors, inflammation, and genetic polymorphisms. Transl Res. 2007;149(3):137-144. doi: https://doi.org/10.1016/j.trsl.2006.09.001
16. Opstad TB, Pettersen AAR, Weiss TW, et al. Genetic variation, gene-expression and circulating levels of matrix metalloproteinase-9 in patients with stable coronary artery disease. Clin Chim Acta. 2012;413(1-2):113-120. doi: https://doi.org/10.1016/j.cca.2011.09.004
17. Hamed GM, Fattah MFA. Clinical Relevance of matrix metalloproteinase 9 in patients with acute coronary syndrome. Clin Appl Thromb Hemost. 2015;21(8):750-754. doi: https://doi.org/10.1177/1076029614567309
18. Fukuda D, Shimada K, Tanaka A, et al. Comparison of levels of serum matrix metalloproteinase-9 in patients with acute myocardial infarction versus unstable angina pectoris versus stable angina pectoris. Am J Cardiol. 2006;97(2):175-180. doi: https://doi.org/10.1016/J.AMJCARD.2005.08.020
19. Garvin P, Jonasson L, Nilsson L, Falk M, Kristenson M. Plasma Matrix Metalloproteinase-9 Levels Predict First-Time Coronary Heart Disease: An 8-Year Follow-Up of a Community-Based Middle Aged Population. PLoS One. 2015;10(9). doi: https://doi.org/10.1371/JOURNAL.PONE.0138290
20. Kobayashi N, Hata N, Kume N, et al. Matrix metalloproteinase-9 for the earliest stage acute coronary syndrome. Circ J. 2011;75(12):2853-2861. doi: https://doi.org/10.1253/CIRCJ.CJ-11-0640
21. Sundström J, Evans JC, Benjamin EJ, et al. Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures: The Framingham heart study. Circulation. 2004;109(23):2850-2856. doi: https://doi.org/10.1161/01.CIR.0000129318.79570.84
22. Kelly D, Cockerill G, Ng LL, et al. Plasma matrix metalloproteinase-9 and left ventricular remodelling after acute myocardial infarction in man: A prospective cohort study. Eur Heart J. 2007;28(6):711-718. doi: https://doi.org/10.1093/eurheartj/ehm003
23. Franz M, Berndt A, Altendorf-Hofmann A, et al. Serum levels of large tenascin-C variants, matrix metalloproteinase-9, and tissue inhibitors of matrix metalloproteinases in concentric versus eccentric left ventricular hypertrophy. Eur J Heart Fail. 2009;11(11):1057-1062. doi: https://doi.org/10.1093/eurjhf/hfp128
24. Saglam M, Karakaya O, Esen AM, et al. Contribution of plasma matrix metalloproteinases to development of left ventricular hypertrophy and diastolic dysfunction in hypertensive subjects. Tohoku J Exp Med. 2006;208(2):117-122. doi: https://doi.org/10.1620/tjem.208.117
25. Ahmed SH, Clark LL, Pennington WR, et al. Matrix metalloproteinases/tissue inhibitors of metalloproteinases: Relationship between changes in proteolytic determinants of matrix composition and structural, functional, and clinical manifestations of hypertensive heart disease. Circulation. 2006;113(17):2089-2096. doi: https://doi.org/10.1161/CIRCULATIONAHA.105.573865
26. Linssen PBC, Brunner-La Rocca HP, Schalkwijk CG, et al. Serum matrix metalloproteinases and left atrial remodeling—the Hoorn study. Int J Mol Sci. 2020;21(14):1-11. doi: https://doi.org/10.3390/ijms21144944
27. Sokolova NA, Danshova MS, Govorin AV, Zaitsev DN, Smolyakov YN. The association of gene polymorphisms of matrix metalloproteinases (-9, -12 and -20) and collagen type I degradation products with the remodeling of the left ventricle in patients with acute myocardial infarction. Kardiologiya. 2018;58(3):13-19. doi: https://doi.org/10.18087/cardio.2018.3.10093
Pogorielova O, Chumachenko YA, Obukhova O, Martsovenko I, Harbuzova V. Coronary artery disease association with serum concentration and genetic variation of MMP-9 in Ukrainian population. Eur Heart J. 2021;42(Supplement_1). doi: https://doi.org/10.1093/EURHEARTJ/EHAB724.1338
Published
2022-09-30
How to Cite
Oksana Pogorielova, Viktoriia Korniienko, Yaroslav Chumachenko, Olha Obukhova, Igor Martsovenko, Andrii Grek, Liudmila Prystupa, & Viktoriia Harbuzova. (2022). ASSOCIATION OF MMP-9 GENETIC POLYMORPHISM AND ММР-9 CONCENTRATION WITH ECHOCARDIOGRAPHIC PARAMETERS IN UKRAINIAN PATIENTS WITH CORONARY ARTERY DISEASE. Eastern Ukrainian Medical Journal, 10(3), 223-232. https://doi.org/10.21272/eumj.2022;10(3):223-232