Study of the diagnostic significance of telomere length in patients with cerebral atherosclerosis

Authors

  • M. S. Yehorova National Academy of Medical Sciences of Ukraine”, Kyiv, https://orcid.org/0000-0002-3689-2683
  • D. S. Krasnienkov SI “Institute of Gerontology named after D. F. Chebotarev of the National Academy of Medical Sciences of Ukraine”, Kyiv,
  • V. H. Hurianov O. O. Bogomolets National Medical University, Kyiv, Ukraine,
  • V. Ye. Kondratiuk O. O. Bogomolets National Medical University, Kyiv, Ukraine,

DOI:

https://doi.org/10.14739/2310-1210.2020.3.204885

Keywords:

telomere length, telomerase activity, cerebral atherosclerosis

Abstract

 

Cerebrovascular diseases are one of the most important causes of morbidity and mortality in the adult population.

Objective to determine the relationship between telomere length and lipid spectrum, structural and functional state of the heart and cerebral vessels and heart rate variability in patients with 1–3 degree cerebral atherosclerosis (CA).

Materials and methods. In a comprehensive clinical and instrumental study, 161 patients with 1–3 degree CA were enrolled. Telomerase activity was determined using a real-time tandem repeat amplification protocol. The relative lengths of telomeres were measured by multiplex quantitative polymerase chain reaction in real time.

Results. Patients were divided into 2 groups: І – with CA of 1–2 degree, ІІ – with CA of 3 degree (who had suffered an ischemic atherothrombotic stroke (AS)). Mean age was 65.1 ± 10.5 and 65.4 ± 9.1 years, respectively. The proportion of men was 21.2 % in group I and 52 % in group II. To identify the factors that influence telomere size as a marker of early aging, the method of constructing logistic regression models was used. In building the models, the following categories were used: shorter telomere length – T/S <2.61 (low and medium tertiles); longer telomere length – T/S over 2.61. For a set of significant risk factors selection, the method of step-by-step inclusion / exclusion of signs was used (stepwise exclusion threshold value of P > 0.15 and inclusion threshold value of P < 0.03). A multivariate logistic regression model was developed based on the identified significant risk factors. A statistically significant positive relationship was found between the telomere length and both the E/A index (diastolic function of the heart) and LPVLD, as well as negative relationship with both the EF and the intima-media complex (IMC) on the right.

Conclusions. Telomere length is comparable in elderly patients with 1–2 degree CA and those who suffered an ischemic atherothrombotic stroke. Based on the multifactor regression analysis, the relationship between telomere length and LPVLD, IMC, EF and LV diastolic function was detected in patients at different stages of CA, including type 2 diabetes (AUC = 0.79 (CI 0.69–0.87)).

 

References

Petrie, A., & Sabin, C. (2009). Medical statistics at a glance (3rd ed.). Wiley-Blackwell.

Banerjee, P. P., & Jagadeesh, S. (2009). Non-Radioactive Assay Methods for the Assessment of Telomerase Activity and Telomere Length. In S. Chellappan (Ed.). Chromatin Protocols. Methods in Molecular Biology (Methods and Protocols), (2nd ed., Vol. 523, pp. 383-394). Humana Press. https://doi.org/10.1007/978-1-59745-190-1_25

Benetos, A., Toupance, S., Gautier, S., Labat, C., Kimura, M., Rossi, P. M., Settembre, N., Hubert, J., Frimat, L., Bertrand, B., Boufi, M., Flecher, X., Sadoul, N., Eschwege, P., Kessler, M., Tzanetakou, I. P., Doulamis, I. P., Konstantopoulos, P., Tzani, A., … Aviv, A. (2018). Short Leukocyte Telomere Length Precedes Clinical Expression of Atherosclerosis. Circulation Research, 122(4), 616-623. https://doi.org/10.1161/circresaha.117.311751

Cawthon, R. M. (2009). Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Research, 37(3), Article e21. https://doi.org/10.1093/nar/gkn1027

Denil, S. L. I. J., Rietzschel, E. R., De Buyzere, M. L., Van daele, C. M., Segers, P., De Bacquer, D., Van Criekinge, W., Bekaert, S., Gillebert, T. C., & De Meyer, T. (2014). On Cross-Sectional Associations of Leukocyte Telomere Length with Cardiac Systolic, Diastolic and Vascular Function: The Asklepios Study. PLOS ONE, 9(12), Article e115071. https://doi.org/10.1371/journal.pone.0115071

Ellehoj, H., Bendix, L., & Osler, M. (2015). Leucocyte Telomere Length and Risk of Cardiovascular Disease in a Cohort of 1,397 Danish Men and Women. Cardiology, 133(3), 173-177. https://doi.org/10.1159/000441819

Jin, X., Pan, B., Dang, X., Wu, H., & Xu, D. (2018). Relationship between short telomere length and stroke. Medicine, 97(39), Article e12489. https://doi.org/10.1097/md.0000000000012489

Collerton, J., Barrass, K., Bond, J., Eccles, M., Jagger, C., James, O., Martin-Ruiz, C., Robinson, L., von Zglinicki, T., & Kirkwood, T. (2007). The Newcastle 85+ study: biological, clinical and psychosocial factors associated with healthy ageing: study protocol. BMC Geriatrics, 7, Article 14. https://doi.org/10.1186/1471-2318-7-14

Khalangot, M., Krasnienkov, D., Vaiserman, A., Avilov, I., Kovtun, V., Okhrimenko, N., Koliada, A., & Kravchenko, V. (2017). Leukocyte telomere length is inversely associated with post-load but not with fasting plasma glucose levels. Experimental Biology and Medicine, 242(7), 700-708. https://doi.org/10.1177/1535370217694096

Laina, A., Stellos, K., & Stamatelopoulos, K. (2018). Vascular ageing: Underlying mechanisms and clinical implications. Experimental Gerontology, 109, 16-30. https://doi.org/10.1016/j.exger.2017.06.007

Lehrer, P. M., & Gevirtz, R. (2014). Heart rate variability biofeedback: how and why does it work? Frontiers in Psychology, 5, Article 756. https://doi.org/10.3389/fpsyg.2014.00756

Koriath, M., Müller, C., Pfeiffer, N., Nickels, S., Beutel, M., Schmidtmann, I., Rapp, S., Münzel, T., Westermann, D., Karakas, M., Wild, P. S., Lackner, K. J., Blankenberg, S., & Zeller, T. (2019). Relative Telomere Length and Cardiovascular Risk Factors. Biomolecules, 9(5), Article 192. https://doi.org/10.3390/biom9050192

Streltsova, L. I., Tkacheva, О. N., Plokhova, E. V., Akasheva, D. U., Strajesko, I. D., Dudinskaya, E. N., & Boytsov, S. А. (2017). Vozrastnye izmeneniya variabel'nosti ritma serdtsa i ikh svyaz' s dlinoi telomer leikotsitov [Age-related changes in heart rate variability and their relation with leucocyte telomere length]. Kardiovaskulyarnaya terapiya i profilaktika, 16(1), 54-60. https://doi.org/10.15829/1728-8800-2017-1-54-60 [in Russian].

Sambrook, J., & Russell, D. W. (2006). Purification of Nucleic Acids by Extraction with Phenol:Chloroform. Cold Spring Harbor Protocols, 2006(1), 169-170. https://doi.org/10.1101/pdb.prot4455

Staerk, L., Wang, B., Lunetta, K. L., Helm, R. H., Ko, D., Sherer, J. A., Ellinor, P. T., Lubitz, S. A., McManus, D. D., Vasan, R. S., Benjamin, E. J., & Trinquart, L. (2017). Association Between Leukocyte Telomere Length and the Risk of Incident Atrial Fibrillation: The Framingham Heart Study. Journal of the American Heart Association, 6(11), Article e006541. https://doi.org/10.1161/jaha.117.006541

Toupance, S., Labat, C., Temmar, M., Rossignol, P., Kimura, M., Aviv, A., & Benetos, A. (2017). Short Telomeres, but Not Telomere Attrition Rates, Are Associated With Carotid Atherosclerosis. Hypertension, 70(2), 420-425. https://doi.org/10.1161/hypertensionaha.117.09354

How to Cite

1.
Yehorova MS, Krasnienkov DS, Hurianov VH, Kondratiuk VY. Study of the diagnostic significance of telomere length in patients with cerebral atherosclerosis. Zaporozhye medical journal [Internet]. 2020Jun.10 [cited 2024Apr.23];22(3). Available from: http://zmj.zsmu.edu.ua/article/view/204885

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Section

Original research