Remodeling and diastolic dysfunction of the left ventricle in patients with arterial hypertension and polymorphism rs5918 of the ITGB3 gene: cross-sectional study

Cover Page

Cite item

Full Text

Abstract

OBJECTIVE: To identify diastolic myocardial function features in late postmenopausal women with polymorphic variants of the integrin beta-3 (ITGB3) gene and arterial hypertension.

MATERIALS AND METHODS: This cross-sectional study enrolled 97 postmenopausal women, with a median age of 67 (65÷70) years. The duration of menopause was 18 (16÷21) years. Molecular genetic studies to assess ITGB3 (rs5918) T1565C polymorphism were performed. The study participants with the homozygous TT ITGB3 polymorphic variant comprised group 1, whereas group 2 included patients with the C allele (TC and CC genotypes). All patients underwent standard transthoracic echocardiography and assessment of left ventricular (LV) diastolic function by transmitral flow. LV diastolic dysfunction was classified into rigid, pseudonormal, and restrictive.

RESULTS: Homozygous allelic variant TT was detected in 65 (67%) patients, heterozygous TC in 29 (30%), and homozygous polymorphic variant CC in 3 (3%). LVDD occurred in all patients included in the study. Among patients with the TT allelic variant of ITGB3, rigid LVDD was diagnosed in 34 (52%), and its pseudo-normal variant was detected in 31 (48%). Among TC and CC genotypes of C allele carriers, a pseudo-normal variant of LVDD (p <0.01), which occurred in 20 (62%) patients, was statistically significantly more frequently recorded, and 12 (38%) patients had a rigid type of LVDD. In addition, a rigid type LVDD was not detected in any case. Calcification of the mitral and aortic valve leaflets was detected in 24 (37%) cases in group 1 and in 9 (28%) patients in group 2 (p=0.68). In fibrous rings, calcifications were found in 34 (52%) patients in group 1 and 16 (50%) in group 2 (p=0.31), and the differences were not statistically significant.

CONCLUSION: This study presents a significant contribution of the rs5918 polymorphism of ITGB3 in the development of myocardial remodeling and LVDD in postmenopausal women.

About the authors

Muraz A. Shambatov

Ural State Medical University

Author for correspondence.
Email: Muraz.shambatov@rambler.ru
ORCID iD: 0000-0001-7312-415X
SPIN-code: 6693-5347
Scopus Author ID: 57216921642

graduate student

Russian Federation, 3 Repina Str., 620028, Ekaterinburg

Nadezhda V. Izmozherova

Ural State Medical University; Institute of High Temperature Electrochemistry, Ural Branch of RAS

Email: nadezhda_izm@mail.ru
ORCID iD: 0000-0001-7826-9657
SPIN-code: 4738-3269
Scopus Author ID: 19337559100

MD, Dr. Sci. (Med.), associate professor

Russian Federation, 3 Repina Str., 620028, Ekaterinburg; Yekaterinburg

Artem A. Popov

Ural State Medical University; Institute of High Temperature Electrochemistry, Ural Branch of RAS

Email: art_popov@mail.ru
ORCID iD: 0000-0001-6216-2468
SPIN-code: 5083-9389
Scopus Author ID: 24390984000

MD, Dr. Sci. (Med.), associate professor

Russian Federation, 3 Repina Str., 620028, Ekaterinburg; Yekaterinburg

Irina F. Grishina

Ural State Medical University

Email: grishif@mail.ru
ORCID iD: 0009-0005-8643-1825
SPIN-code: 5964-0857
Scopus Author ID: 7005557345

MD, Dr. Sci. (Med.), Professor

Russian Federation, 3 Repina Str., 620028, Ekaterinburg

Elena V. Kudryavtseva

Ural State Medical University

Email: elenavladpopova@yandex.ru
ORCID iD: 0000-0003-2797-1926
SPIN-code: 7232-3743
Scopus Author ID: 57211989398

MD, Dr. Sci. (Med.), associate professor

Russian Federation, 3 Repina Str., 620028, Ekaterinburg

References

  1. Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2016;17(12):1321–1360. doi: 10.1093/ehjci/jew082
  2. Chand V. Understanding diastolic dysfunction. JAAPA. 2006;19(3):37–46. doi: 10.1097/01720610-200603000-00006
  3. Obokata M, Reddy YNV, Borlaug BA. Diastolic dysfunction and heart failure with preserved ejection fraction: understanding mechanisms by using noninvasive methods. JACC Cardiovasc Imaging. 2020;13(1 Pt 2):245–257. doi: 10.1016/j.jcmg.2018.12.034
  4. Kalinkina TV, Lareva NV, Chistyakova MV, Gorbunov VV. The Relationship of Endothelial Dysfunction with the Development of Diastolic Heart Failure in Patients with Hypertension. Rational Pharmacotherapy in Cardiology. 2020;16(3):370–376. (In Russ). doi: 10.20996/1819-6446-2020-05-04
  5. Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62(4):263–271. doi: 10.1016/j.jacc.2013.02.092
  6. Rubattu S, Di Angelantonio E, Nitsch D, et al. Polymorphisms in prothrombotic genes and their impact on ischemic stroke in a Sardinian population. Thromb Haemost. 2005;93(6):1095–1100. doi: 10.1160/TH04-07-0457
  7. Di Castelnuovo A, de Gaetano G, Benedetta Donati M, Iacoviello L. Platelet glycoprotein IIb/IIIa polymorphism and coronary artery disease: implications for clinical practice. Am J Pharmacogenomics. 2005;5(2):93–99. doi: 10.2165/00129785-200505020-00002
  8. Islam MR, Nova TT, Momenuzzaman N, et al. Prevalence of CYP2C19 and ITGB3 polymorphisms among Bangladeshi patients who underwent percutaneous coronary intervention. SAGE Open Med. 2021;9:20503121211042209. doi: 10.1177/20503121211042209
  9. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002;110(6):673–687. doi: 10.1016/s0092-8674(02)00971-6
  10. Campbell ID, Humphries MJ. Integrin structure, activation, and interactions. Cold Spring Harb Perspect Biol. 2011;3(3):a004994. doi: 10.1101/cshperspect.a004994
  11. Ruoslahti E, Pierschbacher MD. Arg-Gly-Asp: a versatile cell recognition signal. Cell. 1986;44(4):517–518. doi: 10.1016/0092-8674(86)90259-x
  12. Heinzmann ACA, Karel MFA, Coenen DM, et al. Complementary roles of platelet αIIbβ3 integrin, phosphatidylserine exposure and cytoskeletal rearrangement in the release of extracellular vesicles. Atherosclerosis. 2020;310:17–25. doi: 10.1016/j.atherosclerosis.2020.07.015
  13. Huang WC, Lin KC, Hsia CW, et al. The Antithrombotic Agent Pterostilbene Interferes with Integrin αIIbβ3-Mediated Inside-Out and Outside-In Signals in Human Platelets. Int J Mol Sci. 2021;22(7):3643. doi: 10.3390/ijms22073643
  14. Ashizawa N, Graf K, Do YS, et al. Osteopontin is produced by rat cardiac fibroblasts and mediates A(II)-induced DNA synthesis and collagen gel contraction. J Clin Invest. 1996;98(10):2218–2227. doi: 10.1172/JCI119031
  15. Durrant TN, van den Bosch MT, Hers I. Integrin αIIbβ3 outside-in signaling. Blood. 2017;130(14):1607–1619. doi: 10.1182/blood-2017-03-773614
  16. Baker KM, Booz GW, Dostal DE. Cardiac actions of angiotensin II: Role of an intracardiac renin-angiotensin system. Annu Rev Physiol. 1992;54:227–241. doi: 10.1146/annurev.ph.54.030192.001303
  17. Morkin E, Ashford TP. Myocardial DNA synthesis in experimental cardiac hypertrophy. Am J Physiol. 1968;215(6):1409–1413. doi: 10.1152/ajplegacy.1968.215.6.1409
  18. Weber KT, Janicki JS, Shroff SG, et al. Collagen remodeling of the pressure-overloaded, hypertrophied nonhuman primate myocardium. Circ Res. 1988;62(4):757–765. doi: 10.1161/01.res.62.4.757
  19. Wang X, Khalil RA. Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease. Adv Pharmacol. 2018;81:241–330. doi: 10.1016/bs.apha.2017.08.002
  20. Filippi A, Constantin A, Alexandru N, et al. Integrins α4β1 and αVβ3 are Reduced in Endothelial Progenitor Cells from Diabetic Dyslipidemic Mice and May Represent New Targets for Therapy in Aortic Valve Disease. Cell Transplant. 2020;29:963689720946277. doi: 10.1177/0963689720946277
  21. Misra A, Sheikh AQ, Kumar A, et al. Integrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis. J Exp Med. 2016;213(3):451–463. doi: 10.1084/jem.20150688
  22. Misra A, Feng Z, Chandran RR, et al. Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells. Nat Commun. 2018;9(1):2073. doi: 10.1038/s41467-018-04447-7
  23. Porter TR, Mulvagh SL, Abdelmoneim SS, et al. Clinical Applications of Ultrasonic Enhancing Agents in Echocardiography: 2018 American Society of Echocardiography Guidelines Update. J Am Soc Echocardiogr. 2018;31(3):241–274. doi: 10.1016/j.echo.2017.11.013
  24. Ganau A, Devereux RB, Roman MJ, et al. Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension. J Am Coll Cardiol. 1992;19(7):1550–1558. doi: 10.1016/0735-1097(92)90617-v
  25. Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28(1):1.e14–39.e14. doi: 10.1016/j.echo.2014.10.003
  26. Maslov PZ, Kim JK, Argulian E, et al. Is Cardiac Diastolic Dysfunction a Part of Post-Menopausal Syndrome? JACC Heart Fail. 2019;7(3):192–203. doi: 10.1016/j.jchf.2018.12.018
  27. Johnston RK, Balasubramanian S, Kasiganesan H, et al. Beta3 integrin-mediated ubiquitination activates survival signaling during myocardial hypertrophy. FASEB J. 2009;23(8):2759–2771. doi: 10.1096/fj.08-127480
  28. Willey CD, Balasubramanian S, Rodríguez Rosas MC, et al. Focal complex formation in adult cardiomyocytes is accompanied by the activation of beta3 integrin and c-Src. J Mol Cell Cardiol. 2003;35(6):671–683. doi: 10.1016/s0022-2828(03)00112-3
  29. Anthis NJ, Campbell ID. The tail of integrin activation. Trends Biochem Sci. 2011;36(4):191–198. doi: 10.1016/j.tibs.2010.11.002
  30. Balasubramanian S, Quinones L, Kasiganesan H, et al. β3 integrin in cardiac fibroblast is critical for extracellular matrix accumulation during pressure overload hypertrophy in mouse. PLoS One. 2012;7(9):e45076. doi: 10.1371/journal.pone.0045076
  31. Khutornaya MV, Ponasenko AV, Kutikhin AG, et al. RS10455872 polymorphism within the lpa gene is associated with severe bioprosthetic mitral valve calcification. Medicine in Kuzbass. 2016;4:13–20. (In Russ).
  32. Thanassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013;368(6):503–512. doi: 10.1056/NEJMoa1109034
  33. Babanin VS, Shashina NB, Dokina ED, et al. Aortic valve calcification and calcific aortic stenosis in women. KMJ. 2018;4:59–63. (In Russ).

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Frequency of different types of diastolic dysfunction (ДД) detected in female patients with various polymorphic variants of the ITGB3 gene.

Download (55KB)
Indexing metadata

Copyright (c) 2023 Eco-Vector

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

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies