SALIVA CONCENTRATION OF SIRTUINS: PERSPECTIVES OF APPLICATION FOR CORONARY HEART DISEASE DIAGNOSTICS AND AGING RATE

DOI: https://doi.org/10.29296/24999490-2021-06-06

N.S. Linkova(1–3), A.E. Pychalskaya(3), А.N. Il’nitskii(1, 2), U.А. Novak-Bobarikina(4), О.А. Osipova(1), О.А. Rozhdestvenskaya(1), K.L. Kozlov(3) 1-Belgorod National Research University, Pobedy str., 85, Belgorod, 308009, Russian Federation; 2-Academy of postgraduate education under FSBU FSCC of FMBA of Russia, Volokolamskoe av., 91, Moscow, 125371, Russian Federation; 3-Saint Petersburg Institute of Bioregulation and Gerontology, Dynamo pr., 3, Saint Petersburg, 197110, Russian Federation; 4-Saint-Petersburg State University, Mendeleevskaya line, 2, Saint Petersburg, 199034, Russian Federation E-mail: [email protected]

The aim is the comparative analysis of saliva concentration of sirtuins, in middle age and elderly people without cardiovascular pathology (CP) and with coronary heart disease (CHD). Methods. Saliva was obtained from healthy donors (73 persons without CP, «norm») and 68 CHD patients of middle age and elderly age. Sirt1, Sirt3, Sirt4, Sirt5, Sirt6, Sirt7 concentrations were verified in saliva by enzymoimmunoassay. Results. Sirt1, Sirt6, Sirt7 concentrations in saliva in elderly patients from the group «norm» were 1.5–1.6 times lower in comparison with this value in middle-aged patients. Sirt1, Sirt 3, Sirt6, Sirt7 concentrations in saliva in middle-aged and elderly CHD patients were 1.4–4.2 times lower in comparison with the same values in patients of this age in group «norm». Sirt1, Sirt6, Sirt7 concentrations in saliva in elderly CHD patients were 1.5–2.1 times lower in comparison with these values in middle age CHD patients. Conclusions. The Sirt1, Sirt6, Sirt7 saliva study in healthy middle and old people can be used in a comprehensive assessment of biological age . The estimation of Sirt1, Sirt3, Sirt6, Sirt7 concentration in saliva in middle age and elderly patients may be the perspective predictive method of CHD.
Keywords: 
coronary heart disease, biological age, predictive diagnostic, sirtuins, saliva, aging
Список литературы: 
  1. Scherbakova A.V., Barahovskaja T.V. Hronicheskaja ishemicheskaja bolezn' serdtsa u pozhilyh: posobie dlja vrachej. Irkutsk: RIO GBOU DPO IGMAPO, 2016; 38. [Scherbakova A.V., Barachovskaya T.V. Chronic coronary heart disease in elderly: tutorial for doctors. Irkutsk: RIO GBOY DPO IG MAPO, 2016; 38 (in Russian)].
  2. Proshchaev K.I., Il’nitskii A.N., Kvetnoĭ I.M., Kniaz’kin I.V., Zeziulin P.Ia., Konovalov S.S., Filippov S.V. Changes of the endothelium in cardiovascular pathology in the elderly. Part I. Signal molecules and endothelial functions. Klin. Med. 2007; 85 (11): 9–13.
  3. Solodilova M.A., Medvedeva M.V., Bykanova M.A., Vasil'eva O.V., Ivanov V.P. Polimorfizm gena VEGFA, kurenie i ishemicheskaja bolezn' serdtsa: znachimost' genno-sredovyh vzaimodejstvij dlja razvitija zabolevanija. Nauchnye rezul'taty biomeditsinskih issledovanij. 2020; 6 (3): 350–66. https://doi.org/10.18413/2658-6533-2020-6-3-0-6. [Solodilova M.A., Medvedeva M.V., Bykanova M.A., Vasil’eva O.V., Ivanov V.P. Polymorphism of the VEGFA gene, smoking and coronary heart disease: the significance of geneenvironmental interactions for disease susceptibility. Research Results in Biomedicine. 2020; 6 (3): 350–66. https://doi.org/10.18413/2658-6533-2020-6-3-0-6 (in Russian)].
  4. Saraev G.B., Mironova E.S., Linkova N.S., Bunin V.A, Paltsev M.A., Kvetnoy I.M. Investigation of signal molecules in saliva: prospects of application for diagnostics of myocardial infarction and the aging rate of different age people. Adv. Gerontol. 2019; 32 (3): 364–9.
  5. Pal'tsev M.A., Saraev G.B., Bunin V.A., Belushkina N.N., Popravka E.S., Lin'kova N.S., Kozlov K.L., Sedova E.V., Mursalov S.U., Kvetnoj I.M. Sljuna kak biologicheskij ob'ekt dlja neinvazivnoj molekuljarnoj diagnostiki serdechno-sosudistyh zabolevanij. Molekuljarnaja meditsina. 2018; 16 (5): 3–8. https://doi.org/:10.29296/24999490-2018-05-01 [Paltsev M.A., Saraev G.B., Bunin V.A., Belushkina N.N., Popravka E.S., Linkova N.S., Rozlov K.L., Sedova E.V., Mursalov S.U., Kvetnoy I.M. Saliva as the biological object for non-invasive molecular diagnostic of cardiovaslular diseases. Molecular Medicine. 2018; 16 (5): 3–8. https://doi.org/0.29296/24999490-2018-05-01 (in Russian)].
  6. Chojnowska S., Baran T., Wilinska I., Sienicka P., Cabaj-Wiater I., Knaś M. Human saliva as a diagnostic material. Adv. Med. Sci. 2018; 63 (1): 185–91. https://doi.org/ 10.1016/j.advms.2017.11.002.
  7. Castagnola M., Scarano E., Passali G.C., Messana I., Cabras T., Iavarone F., Di Cintio G., Fiorita A., De Corso E., Paludetti G. Salivary biomarkers and proteomics: future diagnostic and clinical utilities. Acta Otorhinolaryngol. Ital. 2017; 37 (2): 94–101. https://doi.org/10.14639/0392-100X-1598.
  8. Ianni A., Yuan X., Bober E., Braun T. Sirtuins in the Cardiovascular System: Potential Targets in Pediatric Cardiology. Pediatric Cardiology. 2018; 39: 983–92. https://doi.org/10.1007/s00246-018-1848-1.
  9. Pukhalskaia A.E., Dyatlova A.S., Linkova N.S., Kozlov K.L., Kvetnaia T.V., Koroleva M.V., Kvetnoy I.M. Sirtuins as possible predictors of aging in Alzheimer’s disease development: verification in the hippocampus and saliva. Bull. Exp. Biol. Med. 2020; 106 (6): 821–4. https://doi.org/10.1007./s105.17-020-04986-4.
  10. Potthast A.B., Heuer T., Warneke S.J., Das A.M. Alterations of sirtuins in mitochondrial cytochrome c-oxidase deficiency. PLoS ONE. 2017; 12 (10): e0186517. https://doi.org/10.1371/journal.pone.0186517.
  11. Yang B., Xu B., Zhao H., Wang Y.B., Zhang J., Li C.W., Wu Q., Cao Y.K., Li Y., Cao F. Dioscin protects against coronary heart disease by reducing oxidative stress and inflammation via Sirt1/Nrf2 and p38 MAPK pathways. Mol. Med. Rep. 2018; 18 (1): 973–80. https://doi.org/10.3892/mmr.2018.9024.
  12. Yuan X., Qi H., Li X., Wu F., Fang J., Bober E., Dobreva G., Zhou Y,. Braun T. Disruption of spatiotemporal hypoxic signaling causes congenital heart disease in mice. J. Clin. Invest. 2017; 127 (6): 2235–48. https://doi.org/10.1172/JCI88725.
  13. Opstad T.B., Kalstad A.A., Holte K.B., Berg T.J., Solheim S., Arnesen H., Seljeflot I. Shorter Leukocyte Telomere Lengths in Healthy Relatives of Patients with Coronary Heart Disease. Rejuvenation Res. 2020; 23 (4): 324–32. https://doi.org/10.1089/rej.2019.2258.
  14. Du S., Shen S., Ding S., Wang L. Suppression of microRNA-323-3p restrains vascular endothelial cell apoptosis via promoting sirtuin-1 expression in coronary heart disease. Life Sci. 2021; 270: 119065. https://doi.org/10.1016/j.lfs.2021.119065.
  15. Inamori T., Goda T., Kasezawa N., Yamakawa-Kobayashi K. The combined effects of genetic variation in the SIRT1 gene and dietary intake of n-3 and n-6 polyunsaturated fatty acids on serum LDL-C and HDL-C levels: a population based study. Lipids Health Dis. 2013; 12: 4. https://doi.org/10.1186/1476-511X-12-4.
  16. Kida Y., Goligorsky M.S. Sirtuins, Cell Senescence, and Vascular Aging. Can J. Cardiol. 2016; 32 (5): 634–41. https://doi.org/10.1016/j.cjca.2015.11.022.
  17. Bi S., Liu Z., Wu Z., Wang Z., Liu X., Wang S., Ren J., Yao Y., Zhang W., Song M., Liu G.H., Qu J. SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer. J. Protein Cell. 2020; 11 (7): 483–504. https://doi.org/10.1007/s13238-020-00728-4.
  18. Horvath S., Gurven M., Levine M.E., Trumble B.C., Kaplan H., Allayee H., Ritz B.R., Chen B., Lu A.T., Rickabaugh T.M., Jamieson B.D., Sun D., Li S., Chen W., Quintana-Murci L., Fagny M., Kobor M.S., Tsao P.S., Reiner A.P., Edlefsen K.L., Absher D., Assimes T.L. An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease. Genome Biol. 2016; 17 (1): 171. https://doi.org/10.1186/s13059-016-1030-0.
  19. Al-Rawi N.H., Shahid A.M. Oxidative stress, antioxidants, and lipid profile in the serum and saliva of individuals with coronary heart disease: is there a link with periodontal health? Minerva Stomatol. 2017; 66 (5): 212–25. https://doi.org/10.23736/S0026-4970.17.04062-6.
  20. McGeer P.L., Lee M., Kennedy K., McGeer E.G. Saliva Diagnosis as a Disease Predictor. J. Clin. Med. 2020; 9 (2): 377. https://doi.org/10.3390/jcm9020377.
  21. Mahmood Z., Enocsson H., Bäck M., Chung R.W.S., Lundberg A.K., Jonasson L. Salivary and plasma levels of matrix metalloproteinase-9 and myeloperoxidase at rest and after acute physical exercise in patients with coronary artery disease. PLoS One. 2019; 14 (2): e0207166. https://doi.org/10.1371/journal.pone.0207166.
  22. Fic P., Kowalczuk K., Grabarska A., Stepulak A. MicroRNA--a new diagnostic tool in coronary artery disease and myocardial infarction. Postepy Hig Med Dosw. 2014; 68: 410–8. https://doi.org/0.5604/17322693.1100348.
  23. Prestes P.R., Maier M.C., Woods B.A., Charchar F.J. A Guide to the Short, Long and Circular RNAs in Hypertension and Cardiovascular Disease. Int. J. Mol Sci. 2020; 21(10): 3666. https://doi.org/0.3390/ijms21103666