Clinical importance of evaluation of circulating miRNA expression and epicardial adipose tissue thickness as predictors of cardiovascular pathology in young patients with type 1 diabetes mellitus
- Authors: Vengrzhinovskaya O.I.1, Bondarenko I.Z.1, Shatskaya O.A.1, Tarbaeva N.V.1, Korneluk A.Y.1, Kalashnikov V.Y.1, Shestakova M.V.1, Mokrysheva N.G.1
-
Affiliations:
- National Medical Research Center for Endocrinology
- Issue: Vol 95, No 10 (2023)
- Pages: 839-844
- Section: Original articles
- URL: https://journals.rcsi.science/0040-3660/article/view/254721
- DOI: https://doi.org/10.26442/00403660.2023.10.202426
- ID: 254721
Cite item
Full Text
Abstract
Cardiovascular disease (CVD) in type 1 diabetes mellitus (T1DM) is preceded by asymptomatic changes in the geometry of the heart. The only symptoms of the beginning of cardiac remodeling and concomitant predictors of an unfavorable cardiovascular prognosis are: thickening of epicardial fat (EAT), secreting a number of adipokines, and cardiospecific miRNAs. To improve the effectiveness of prevention of CVD in young patients with DM1, a search was made for structural-functional and epigenetic markers.
Aim. To assess the state of the cardiovascular system according to MRI-heart with T1 mapping in T1DM without CVD. To reveal the relationship of epigenetic markers (circulating miR-126-5p, miR-21-5p) and adipokines with cardiovascular system in T1DM. Suggested personalized approach to patients with T1DM with initial manifestations of joint remodeling and/or exclusion of cardiospecific microRNA.
Materials and methods. The study included 40 patients: 30 with T1DM (age 26.2±7.4 years), 10 without T1DM (26.4±8.2). The patients underwent a general clinical examination, bioimpedancemetry, electrocardiography, MRI of the heart with T1 mapping, determination of adiponectin, resistin, visfatin, NT-proBNP, miR-126-5p, miR-21-5p.
Results. Patients with T1DM had lower levels of cardioprotective miR-126-5p (p=0.046). According to MRI of the heart in T1DM, signs of vascular remodeling were revealed – thickening of the interventricular septum (p=0.001), posterior wall (p=0.012) and relative size of the walls (p=0.048) of the left ventricle, an increase in EAT density (p=0.001). Diffuse vascular fibrosis was found in 16% of patients from the T1DM group. Also, in T1DM, the expression of visfatin is increased (p=0.036) and adiponectin is reduced (p=0.043).
Conclusion. Structural and functional changes in the cardiovascular system (including thickening of the EAT), shifts in miR-126-5p expression and adipokines profile are observed already at a young age in patients with T1DM. In T1DM, diffuse vascular fibrosis is detected in 16% of patients. The data obtained were used to identify the group increased risk of developing CVD in T1DM and served as the basis for determining the timing of the start of preventive therapy.
Full Text
##article.viewOnOriginalSite##About the authors
Oksana I. Vengrzhinovskaya
National Medical Research Center for Endocrinology
Author for correspondence.
Email: vengrzhinovskay@gmail.com
ORCID iD: 0000-0003-3370-8630
врач-эндокринолог отд. координации оказания стационарной помощи
Russian Federation, MoscowIrina Z. Bondarenko
National Medical Research Center for Endocrinology
Email: iz_bondarenko@mail.ru
ORCID iD: 0000-0002-5178-6029
д-р мед. наук, врач-кардиолог, гл. науч. сотр. отд. кардиологии и сосудистой хирургии
Russian Federation, MoscowOlga A. Shatskaya
National Medical Research Center for Endocrinology
Email: shatskaya@bk.ru
ORCID iD: 0000-0003-1831-8052
канд. мед. наук, врач-эндокринолог, науч. сотр. отд. кардиологии и сосудистой хирургии
Russian Federation, MoscowNatalia V. Tarbaeva
National Medical Research Center for Endocrinology
Email: sburyakina@yandex.ru
ORCID iD: 0000-0001-7965-9454
канд. мед. наук, врач-рентгенолог, зав. отд-нием компьютерной и магнитно-резонансной томографии
Russian Federation, MoscowAnastasya Y. Korneluk
National Medical Research Center for Endocrinology
Email: korneluk.anastasya@mail.ru
ORCID iD: 0009-0007-4475-8752
врач-рентгенолог отд-ния компьютерной и магнитно-резонансной томографии
Russian Federation, MoscowVictor Y. Kalashnikov
National Medical Research Center for Endocrinology
Email: kosharnaya.raisa@mail.ru
ORCID iD: 0000-0001-5573-0754
чл.-кор. РАН, д-р мед. наук, проф., врач-кардиолог, зам. дир. Центра по координации эндокринологической службы, зав. отд. кардиологии и сосудистой хирургии
Russian Federation, MoscowMarina V. Shestakova
National Medical Research Center for Endocrinology
Email: nephro@endocrincentr.ru
ORCID iD: 0000-0003-3893-9972
акад. РАН, д-р мед. наук, проф., врач-эндокринолог, дир. Института диабета, зам. дир.
Russian Federation, MoscowNatalia G. Mokrysheva
National Medical Research Center for Endocrinology
Email: mokrisheva.natalia@endocrincentr.ru
ORCID iD: 0000-0002-9717-9742
SPIN-code: 5624-3875
чл.-кор. РАН, д-р мед. наук, проф., врач-эндокринолог, врач высшей квалификационной категории, зав. каф. персонализированной и трансляционной медицины, дир.
Russian Federation, MoscowReferences
- Дедов И.И., Шестакова М.В., Викулова О.К., и др. Эпидемиологические характеристики сахарного диабета в Российской Федерации: клинико-статистический анализ по данным регистра сахарного диабета на 01.01.2021. Сахарный диабет. 2021;24(3):204-21 [Dedov II, Shestakova MV, Vikulova OK, et al. Epidemiological characteristics of diabetes mellitus in the Russian Federation: clinical and statistical analysis according to the diabetes register data as of 01.01.2021. Diabetes Mellitus. 2021;24(3):204-21 (in Russian)]. doi: 10.14341/DM12759
- Шестакова М.В., Викулова О.К., Исаков М.А., Дедов И.И. Сахарный диабет и COVID-19: анализ клинических исходов по данным регистра сахарного диабета Российской Федерации. Проблемы эндокринологии. 2020;66(1):35-46 [Shestakova MV, Vikulova OK, Isakov MA, Dedov II. Diabetes and COVID-19: analysis of the clinical outcomes according to the data of the Russian Diabetes Registry. Probl Endokrinol (Mosk). 2020;66(1):35-46 (in Russian)]. doi: 10.14341/probl12458
- Баев М.С., Рыжков А.В., Гаврилова Е.А., Труфанов Г.Е. Клиническое применение Т1-картирования миокарда: обзор литературы и первый опыт клинического применения. Сибирский журнал клинической и экспериментальной медицины. 2022;37(1):17-26 [Baev MS, Ryzhkov AV, Gavrilova EA, Trufanov GE. Clinical application of T1 mapping of the myocardium: a review of the literature and the first experience of clinical application. The Siberian Journal of Clinical and Experimental Medicine. 2022;37(1):17-26 (in Russian)]. doi: 10.29001/2073-8552-2022-37-1-17-26
- Reiter G, Reiter C, Kräuter C, et al. Cardiac magnetic resonance T1 mapping. Part 1: Aspects of acquisition and evaluation. Eur J Radiol. 2018;109:223-34. doi: 10.1016/j.ejrad.2018.10.011
- Baker AR, Silva NF, Quinn DW, et al. Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease. Cardiovasc Diabetol. 2006;5:1. doi: 10.1186/1475-2840-5-1
- Мустафина И.А., Ионин В.А., Долганов А.А., и др. Роль эпикардиальной жировой ткани в развитии сердечно-сосудистых заболеваний. Российский кардиологический журнал. 2022;27(1S):4872 [Mustafina IA, Ionin VA, Dolganov AA, et al. Role of epicardial fat tissue in the development of cardiovascular diseases. Russian Journal of Cardiology. 2022;27(1S):4872 (in Russian)]. doi: 10.15829/1560-4071-2022-4872
- Fu Y, Luo N, Klein RL, Garvey WT. Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J Lipid Res. 2005;46(7):1369-79. doi: 10.1194/jlr.M400373-JLR200
- Malavazos AE, Di Leo G, Secchi F, et al. Relation of echocardiographic epicardial fat thickness and myocardial fat. Am J Cardiol. 2010;105(12):1831-5. doi: 10.1016/j.amjcard.2010.01.368
- Bailey SD, Loredo-Osti JC, Lepage P, et al. Common polymorphisms in the promoter of the visfatin gene (PBEF1) influence plasma insulin levels in a French-Canadian population. Diabetes. 2006;55(10):2896-902. doi: 10.2337/db06-0189
- Moon B, Kwan JJ-M, Duddy N, et al. Resistin inhibits glucose uptake in L6 cells independently of changes in insulin signaling and GLUT4 translocation. Am J Physiol Endocrinol. Metab. 2003;285(1):E106-15. doi: 10.1152/ajpendo.00457.2002
- Mahabadi AA, Massaro JM, Rosito GA, et al. Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study. Eur Heart J. 2009;30(7):850-6. doi: 10.1093/eurheartj/ehn573
- Ding J, Hsu FC, Harris TB, et al. The association of pericardial fat with incident coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr. 2009;90(3):499-504. doi: 10.3945/ajcn.2008.27358
- Ambale-Venkatesh B, Armstrong AC, Liu CY, et al. Diastolic function assessed from tagged MRI predicts heart failure and atrial fibrillation over an 8-year follow-up period: the multi-ethnic study of atherosclerosis. Eur Heart J Cardiovasc Imaging. 2014;15(4):442-9. doi: 10.1093/ehjci/jet189
- Bozkurt B, Coats AJ, Tsutsui H, et al. Universal Definition and Classification of Heart Failure: A Report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure. J Card Fail. 2021;S1071-9164(21)00050-6. doi: 10.1016/j.cardfail.2021.01.022
- Гареев И.Ф., Бейлерли О.А. Циркулирующие микроРНК как биомаркеры: какие перспективы? Профилактическая медицина. 2018;21(6):142-50 [Gareev IF, Beylerli OA. Circulating microRNAs as biomarkers: what are perspectives? Profilakticheskaya Meditsina. 2018;21(6):142-50 (in Russian)]. doi: 10.17116/profmed201821061142
- Nazari-Jahantigh M, Egea V, Schober A, Weber C. MicroRNA-specific regulatory mechanisms in atherosclerosis. J Mol Cell Cardiol. 2015;89(Pt. A):35-41. doi: 10.1016/j.yjmcc.2014.10.021
- Zhang Y, Yuan B, Xu Y, et al. MiR-208b/miR-21 Promotes the Progression of Cardiac Fibrosis Through the Activation of the TGF-β1/Smad-3 Signaling Pathway: An in vitro and in vivo Study. Front Cardiovasc Med. 2022;9:924629. doi: 10.3389/fcvm.2022.924629
- Стоногина Д.А., Желанкин А.В., Аксельрод А.С., и др. Циркулирующие микроРНК как биомаркеры риска сердечно-сосудистых осложнений у больных с ИБС: достижения и трудности последних лет. Кардиология и сердечно-сосудистая хирургия. 2019;12(1):17-24 [Stonogina DA, Zhelankin AV, Akselrod AS, et al. Circulating microRNAs as biomarkers of the risk of cardiovascular complications in patients with coronary artery disease: achievements and difficulties in recent years. Cardiology and Cardiovascular Surgery. 2019;12(1):17-24 (in Russian)]. doi: 10.17116/kardio20191201117
- Sothivelr V, Hasan MY, Saffian SM, et al. Revisiting miRNA-21 as a Therapeutic Strategy for Myocardial Infarction: A Systematic Review. J Cardiovasc Pharmacol. 2022;80(3):393-406. doi: 10.1097/FJC.0000000000001305
- Moghaddam AS, Afshari JT, Esmaeili SA, et al. Cardioprotective microRNAs: Lessons from stem cell-derived exosomal microRNAs to treat cardiovascular disease. Atherosclerosis. 2019;285:1-9. doi: 10.1016/j.atherosclerosis.2019.03.016
Supplementary files
![](/img/style/loading.gif)