Telomere length as a biomarker of the risk of cardiovascular complications in patients with coronary heart disease

Cover Page

Cite item

Full Text

Abstract

Aim. To study the effect of oxidative stress and telomere length in the chromosomes of blood leukocytes in patients with coronary heart disease (CHD) on the development of cardiovascular complications.

Materials and methods. In 119 patients with CHD, the level of oxidatively modified low-density lipoproteins (ox-LDL) in blood plasma and the length of telomeres in nuclear blood cells were determined during the examination. After 5 years, a telephone survey of patients (or their relatives) was conducted to obtain data on the presence of cardiovascular complications. Telomere length was determined using quantitative real-time PCR, and the level of ox-LDL was determined by immunochemical method.

Results. It was found that reducing the length of telomeres in patients with CHD increases the risk of subsequent development of cardiovascular complications. A strong negative correlation was found between the level of ox-LDL and telomere length in the group of examined CHD patients who had cardiovascular complications after 5 years.

Conclusion. CHD patients with short telomere length and high levels of ox-LDL have an increased risk of cardiovascular complications during 5 years.

About the authors

Natalia A. Doroshchuk

National Medical Research Center of Cardiology

Email: lankin0309@mail.ru
ORCID iD: 0000-0003-2258-6463

к.м.н., науч. сотр. отд. биохимии свободнорадикальных процессов

Russian Federation, 15a, 3rd Cherepkovskaya street, Moscow, 121552

Vadim Z. Lankin

National Medical Research Center of Cardiology

Author for correspondence.
Email: lankin0309@mail.ru
ORCID iD: 0000-0002-8018-0296

д.б.н., проф., гл. науч. сотр., рук. отд. биохимии свободнорадикальных процессов

Russian Federation, 15a, 3rd Cherepkovskaya street, Moscow, 121552

Alla K. Tikhaze

National Medical Research Center of Cardiology

Email: lankin0309@mail.ru
ORCID iD: 0000-0003-3870-9923

д.м.н., проф., гл. науч. сотр. отд. биохимии свободнорадикальных процессов

Russian Federation, 15a, 3rd Cherepkovskaya street, Moscow, 121552

Grigory I. Kheimets

National Medical Research Center of Cardiology

Email: lankin0309@mail.ru

к.б.н., ст. науч. сотр. отд. новых методов диагностики

Russian Federation, 15a, 3rd Cherepkovskaya street, Moscow, 121552

Alexander D. Doroshсhuk

National Medical Research Center of Cardiology

Email: lankin0309@mail.ru
ORCID iD: 0000-0002-1547-4693

к.б.н., науч. сотр. отд. биохимии свободнорадикальных процессов

Russian Federation, 15a, 3rd Cherepkovskaya street, Moscow, 121552

Maria D. Smirnova

National Medical Research Center of Cardiology

Email: lankin0309@mail.ru
ORCID iD: 0000-0001-6515-3882

д.м.н, ст. науч. сотр. отд. амбулаторных лечебно-диагностических технологий

Russian Federation, 15a, 3rd Cherepkovskaya street, Moscow, 121552

Irina E. Chazova

National Medical Research Center of Cardiology

Email: lankin0309@mail.ru
ORCID iD: 0000-0001-5215-4894

акад. РАН, проф., д.м.н., зам. ген. дир. по научно-экспертной работе, рук. отд. гипертонии Института клинической кардиологии им. А.Л. Мясникова

Russian Federation, 15a, 3rd Cherepkovskaya street, Moscow, 121552

References

  1. Ланкин В.З., Тихазе А.К., Беленков Ю.Н. Свободнорадикальные процессы при заболеваниях сердечно-сосудистой системы. Кардиология. 2004;44(2):72-81 [Lankin VZ, Tikhaze AK, Belen- kov YuN. Free radical processes in diseases of the cardiovascular system. Kardiologiia. 2004;44(2):72-81 (In Russ.)].
  2. Ланкин В.З., Тихазе А.К. Свободнорадикальные процессы играют важную роль в этиологии и патогенезе атеросклероза и диабета. Кардиология. 2016;56(12):97-105 [Lankin VZ, Tik- haze AK. Free Radical Processes Play an Important Role in the Etiology and Pathogenesis of Atherosclerosis and Diabetes. Kardiologiia. 2016;56(12):97-105 (In Russ.)]. doi: 10.18565/cardio.2016.12. 97-105
  3. Lankin VZ, Tikhaze AK. Role of Oxidative Stress in the Genesis of Atherosclerosis and Diabetes Mellitus: A Personal Look Back on 50 Years of Research. Curr Aging Sci. 2017;10(1):18-25. doi: 10.2174/ 1874609809666160926142640
  4. Coluzzi E, Leone S, Sgura A. Oxidative Stress Induces Telomere Dysfunction and Senescence by Replication Fork Arrest. Cells. 2019;8(1):E19. doi: 10.3390/cells8010019
  5. Дорощук Н.А., Тихазе А.К., Ланкин В.З., и др. Влияние окислительного стресса на длину теломерных повторов в хромосомах лейкоцитов крови лиц с различным риском сердечно-сосудистой смерти и больных ИБС. Кардиологический вестн. 2017;1:32-6 [Doroshchuk NA, Tikhaze AK, Lankin VZ, et al. The influence of oxidative stress on the length of telomeric repeats in the white blood cell chromosomes of individuals with different risks of cardiovascular death and patients with coronary artery disease. Kardiologicheskij vestn. 2017;1:32-6 (In Russ.)].
  6. Rezvan А. Telomeres, oxidative stress, and myocardial infarction. Eur Heart J. 2017;38(41):3105-7. doi: 10.1093/eurheartj/ehx305
  7. Дорощук Н.А., Ланкин В.З., Тихазе А.К., и др. Окислительный стресс и укорочение теломеров в лейкоцитах крови больных с впервые выявленным сахарным диабетом 2 типа. Кардиологический вестн. 2016;2:62-7 [Doroshchuk NA, Lankin VZ, Tikhaze AK, et al. Oxidative stress and telomere shortening in in leukocytes of the blood of patients with newly diagnosed type 2 diabetes. Kardiologicheskij vestn. 2016;2:62-7 (In Russ.)].
  8. Willeit P, Raschenberger J, Heydon EE, et al. Leucocyte Telomere Length and Risk of Type 2 Diabetes Mellitus: New Prospective Cohort Study and Literature-Based Meta-Analysis. PLoS One. 2014;9(11):e112483. doi: 10.1371/journal.pone.0112483
  9. Bernadotte A, Mikhelson VM, Spivak IM. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence. Aging (Albany NY). 2016;8(1):3-11. doi: 10.18632/aging.100871
  10. Arsenis NC, You T, Ogawa EF, et al. Physical activity and telomere length: Impact of aging and potential mechanisms of action. Oncotarget. 2017;8(27):45008-19. doi: 10.18632/oncotarget.16726
  11. Martens DS, Nawrot TS. Air Pollution Stress and the Aging Phenotype: The Telomere Connection. Curr Environ Health Rep. 2016;3(3):258-69. doi: 10.1007/s40572-016-0098-8
  12. Дорощук Н.А., Постнов А.Ю., Дорощук А.Д., и др. Прямое повреждающее воздействие на ДНК человека неблагоприятных экологических и климатических факторов. Терапевтический архив. 2014;86(12):72-7 [Doroshchuk NA, Postnov AIu, Doroshchuk AD, et al. Direct human DNA damage by unfavorable environmental and climatic factors. Terapevticheskii Arkhiv (Ter. Arkh.). 2014;86(12):72-7 (In Russ.)]. doi: 10.17116/terarkh2014861272-77
  13. Astuti Y, Wardhana A, Watkins J, Wulaningsih W. PILAR Research Network. Cigarette smoking and telomere length: A systematic review of 84 studies and meta-analysis. Environ Res. 2017;158:480-9. doi: 10.1016/j.envres.2017.06.038
  14. Rizvi S, Raza ST, Mahdi F. Telomere length variations in aging and age-related diseases. Curr Aging Sci. 2014;7(3):161-7. doi: 10.2174/1874609808666150122153151
  15. Martínez P, Blasco MA. Heart-Breaking Telomeres. Circ Res. 2018;123(7):787-802. doi: 10.1161/CIRCRESAHA.118.312202
  16. Singh A, Kukreti R, Saso L, Kukreti S. Oxidative Stress: Role and Response of Short Guanine Tracts at Genomic Locations. Int J Mol Sci. 2019;20(17):4258. doi: 10.3390/ijms20174258
  17. Wareed A, Lingner J. Impact of oxidative stress on telomere biology. Differentiation. 2018;99:21-7. doi: 10.1016/j.diff.2017.12.002
  18. Cawthon RM. Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res. 2009;37(3):e21. doi: 10.1093/nar/gkn1027
  19. Khlebus E, Kutsenko V, Meshkov A, et al. Multiple rare and common variants in APOB gene locus associated with oxidatively modified low-density lipoprotein levels. PLoS One. 2019;14(5):e0217620. doi: 10.1371/journal.pone.0217620
  20. Lankin VZ, Tikhaze AK, Kumskova EM. Macrophages actively accumulate malonyldialdehyde-modified but not enzymatically oxidized low density lipoprotein. Mol Cell Biochem. 2012;365(1-2):93-8. doi: 10.1007/s11010-012-1247-5
  21. Гречникова М.А., Домогатский С.П., Коновалова Г.Г., и др. Клиренс карбонил-модифицированных липопротеидов из кровотока кроликов. Бюлл. Восточно-Сибирского НЦ СО РАМН. 2016;1(109):104-8 [Grechnikova MA, Domogatsky SP, Konovalo- va GG, et al. Clearance of carbonyl-modified lipoproteins from the bloodstream of rabbits. Biull. Vostochno-Sibirskogo NTs SO RAMN. 2016;1(109):104-8 (In Russ.)].
  22. Ланкин В.З., Тихазе А.К., Вийгимаа М., Чазова И.Е. Ингибитор PCSK9 вызывает снижение уровня окислительно модифицированных липопротеидов низкой плотности у пациентов с ишемической болезнью сердца. Терапевтический архив. 2018;90(9):27-30 [Lankin VZ, Tikhaze AK, Viigimaa M, Chazova IЕ. PCSK9 Inhibitor causes a decrease in the level of oxidatively modified low-density lipoproteins in patients with coronary artery diseases. Terapevticheskii Arkhiv (Ter. Arkh.). 2018;90(9):27-30 (In Russ.)]. doi: 10.26442/terarkh201890927-30

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. The initial length of telomeric repeats of chromosomes (1) and the initial level of ok-LDL (2) in the blood of examined patients with coronary artery disease, who did not experience cardiovascular incidents over the next 5 years (light bars, taken as 100%), and in the group of patients with coronary artery disease, who have been identified within 5 years of CVA: stroke, MI and lethal cases (dark bars). * Differences between the groups without SSO and with SSO are statistically significant at p <0.05.

Download (29KB)
3. Fig. 2. The initial values of the length of telomeric chromosome repeats in the group of examined persons with various cardiovascular events that occurred within 5 years: 1 - without complications, 2 - stroke, 3 - MI, 4 - cardiovascular death. * Indicators in groups 2–4 statistically significantly differ from those in group 1 (without CVC) at p <0.05.

Download (23KB)
4. Fig. 3. Correlation dependence between the initial length of telomeric repeats in the chromosomes of leukocytes and the initial level of blood plasma ok-LDL in patients with coronary artery disease, who did not develop CVC within 5 years after the examination.

Download (42KB)
5. Fig. 4. Correlation dependence between the initial length of telomeric repeats in the chromosomes of leukocytes and the initial level of ok-LDL in blood plasma in patients with coronary artery disease, in whom, within 5 years after the examination, various (CVA, MI, death) were recorded.

Download (37KB)
6. Fig. 5. ROC-curve for determining the predictive value of telomere length in the development of CVO. Area under the curve 0.66; sensitivity 74.3, specificity 57.1 with telomere length less than 61.4 relative units.

Download (45KB)
7. Fig. 6. ROC-curve to determine the predictive value of ok-LDL in the development of CVC (explanations are given in the text of the article).

Download (39KB)

Copyright (c) 2021 Consilium Medicum

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


This website uses cookies

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

About Cookies