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Эпигенетические механизмы кардиопротекции: в фокусе – активация сиртуинов

https://doi.org/10.20514/2226-6704-2021-11-6-424-432

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Аннотация

Окислительный стресс является общим признаком старения и сердечно-сосудистых заболеваний (ССЗ), включая атеросклероз, сердечную недостаточность, гипертонию, сахарный диабет и другие заболевания сосудистой системы. В этой связи, в последние годы исследователи проявляют повышенный интерес к сиртуинам (SIRT) — адаптерам стресса и эпигенетическим ферментам, участвующим в клеточных механизмах контроля возрастных патологий, рака и ССЗ. Среди сиртуинов, которых у млекопитающих семь (SIRT1-SIRT7), кардиопротекторными, противовоспалительными, атеропротекторными и антивозрастными свойствами в наибольшей степени обладают SIRT1 и SIRT6. В данном обзоре мы представляем всесторонний анализ последних событий в области клеточных и молекулярных сигнальных путей, контролируемых двумя посттрансляционными модификаторами — SIRT1 и SIRT6, которые доказали свою ценность в качестве инструментов для ослабления воспаления и окислительного стресса на уровне сердечно-сосудистой системы. Более глубокое понимание эпигенетических механизмов, через которые оказывают своё кардиопротекторное действие SIRT1 и SIRT6, будет иметь широкие последствия и ускорит разработку селективных и эффективных фармакологических препаратов для модуляции сиртуинов с целью профилактики и лечения ССЗ.

Об авторах

К. А. Айтбаев
Научно-исследовательский институт молекулярной биологии и медицины
Кыргызстан

Илхом Торобекович Муркамилов

Бишкек



И. Т. Муркамилов
Кыргызская государственная медицинская академия имени И.К. Ахунбаева; ГОУ ВПО Кыргызско-Российский славянский университет
Кыргызстан

Бишкек



Ж. А. Муркамилова
ГОУ ВПО Кыргызско-Российский славянский университет
Кыргызстан

Бишкек



И. О. Кудайбергенова
Кыргызская государственная медицинская академия имени И.К. Ахунбаева
Кыргызстан

Бишкек



Ф. А. Юсупов
Ошский государственный университет
Кыргызстан

Ош



Список литературы

1. Kazantsev AG and Outeiro TF. Editorial on special topic: sirtuins in metabolism, aging, and disease. Front Pharmacol. 2012; 3: 71. https://doi.org/10.3389/fphar.2012.00071

2. Elibol B and Kilic U. High Levels of SIRT1 as a Protective Mechanism Against Disease-Related Conditions. Front. Endocrinol (Lausanne). 2018; 9: 614. https://doi.org/10.3389/fendo.2018.00614.

3. Hashimoto-Komatsu A, Hirase T, Asaka M et al. Angiotensin II induces microtubule reorganization mediated by a deacetylase SIRT2 in endothelial cells. Hypertens Res. 2011; 34: 949–956. https://doi.org/10.1038/hr.2011.64

4. Kumar S and Lombard DB. Mitochondrial sirtuins and their relationships with metabolic disease and cancer. Antioxid Redox Signal. 2015; 22(12): 1060–1077. https://doi.org/10.1089/ars.2014.6213

5. Bindu S, Pillai VB, and Gupta MP. Role of sirtuins in regulating pathophysiology of the heart. Trends Endocrinol Metab. 2016; 27(8): 563–573. https://doi.org/10.1016/j.tem.2016.04.015

6. Balestrieri ML, Rizzo MR, Barbieri M, et al. Sirtuin 6 expression and inflammatory activity in diabetic atherosclerotic plaques: effects of incretin treatment. Diabetes. 2015; 64(4): 1395–1406. https://doi.org/10.2337/db14-1149

7. de Nigris F, Balestrieri ML, and Napoli C. Targeting cMyc, Ras and IGF cascade to treat cancer and vascular disorders. Cell Cycle. 2006; 5: 1621–1628. https://doi.org/10.4161/cc.5.15.3138

8. Lee IH. Mechanisms and disease implications of sirtuin-mediated autophagic regulation. Exp.Mol. Med. 2019; 51: 102. https://doi.org/10.1038/s12276-019-0302-7

9. Arunachalam G, Sundar IK, Hwang JW et al. Emphysema is associated with increased inflammation in lungs of atherosclerosis-prone mice by cigarette smoke: implications in comorbidities of COPD. J Inflamm (Lond). 2010; 7: 34. https://doi.org/10.1186/1476-9255-7-34

10. Zhang QJ, Wang Z, Chen HZ, et al. Endotheliumspecific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Cardiovasc Res. 2008; 80: 191–199. https://doi.org/10.1093/cvr/cvn224.

11. Napoli C, Balestrieri ML, Sica V, et al. Beneficial effects of low doses of red wine consumption on perturbed shear stress-induced atherogenesis. Heart Vessels. 2008; 23(2): 124–133. https://doi.org/10.1007/s00380-007-1015-8

12. Arunachalam G, Yao H, Sundar IK, Caito S, and Rahman I. SIRT1 regulates oxidant- and cigarette smoke-induced eNOS acetylation in endothelial cells: role of resveratrol. Biochem Biophys Res Commun. 2010; 393: 66–72. https://doi.org/10.1016/j.bbrc.2010.01.080

13. Li L, Zhang HN, Chen HZ, et al. SIRT1 acts as a modulator of neointima formation following vascular injury in mice. Circ Res. 2011; 108: 1180–1189. https://doi.org/10.1016/j.bbrc.2012.10.043

14. Cardellini M, Menghini R, Martelli E, et al. TIMP3 is reduced in atherosclerotic plaques from subjects with type 2 diabetes and increased by SirT1. Diabetes. 2009; 58: 2396– 2401. https://doi.org/10.1016/j.bbrc.2012.10.043

15. Wen L, Chen Z, Zhang F, et al. Ca2+/ calmodulin-dependent protein kinase kinase beta phosphorylation of Sirtuin 1 in endothelium is atheroprotective. Proc Natl Acad Sci U S A. 2013; 110: 26:E2420–E2427. https://doi.org/10.1073/pnas.1309354110

16. Hung CH, Chan SH, Chu PM et al. Quercetin is a potent antiatherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation. Mol Nutr Food Res. 2015; 59(10): 1905–1917. https://doi.org/10.1002/mnfr.201500144

17. Chen ML, Yi L, Jin X, et al. Resveratrol attenuates vascular endothelial inflammation by inducing autophagy through the cAMP signaling pathway. Autophagy. 2013; 9(12): 2033–2045. https://doi.org/10.4161/auto.26336

18. Zhang Y, Sun J, Yu X, et al. SIRT1 regulates accumulation of oxidized LDL in HUVEC via the autophagy-lysosomal pathway. Prostaglandins Other Lipid Mediat. 2016; 122: 37–44. https://doi.org/10.1016/j.prostaglandins.2015.12.005

19. Ming GF, Tang YJ, Hu K, et al. Visfatin attenuates the ox-LDLinduced senescence of endothelial progenitor cells by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway. Int J Mol Med. 2016; 38(2): 643–649. https://doi.org/10.3892/ijmm.2016.2633

20. Stein S, Lohmann C, Scha¨fer N, et al. SIRT1 decreases Lox-1-mediated foam cell formation in atherogenesis. Eur Heart J. 2010; 31(18): 2301–2309. https://doi.org/10.1093/eurheartj/ehq107

21. Ma L, Liu X, Zhao Y, et al. Ginkgolide B reduces LOX-1 expression by inhibiting Akt phosphorylation and increasing Sirt1 expression in oxidized LDL-stimulated human umbilical vein endothelial cells. PLoS One. 2013; 8:9.e74769. https://doi.org/10.1371/journal.pone.0074769

22. Akhmedov A, Camici GG, Reiner MF, et al. Endothelial LOX- 1 activation differentially regulates arterial thrombus formation depending on oxLDL Levels: role of the Oct-1/ SIRT1 and ERK1/2 pathways. Cardiovasc Res. 2017; 113(5): 498– 507. https://doi.org/10.1093/cvr/cvx015

23. Li X, Zhang S, Blander G, et al. SIRT1 deacetylates and positively regulates the nuclear receptor LXR. Mol Cell. 2007; 28(1): 91–106. https://doi.org/10.1016/j.molcel.2007.07.032

24. Kim HS, Xiao C, Wang RH, et al. Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis. Cell Metab. 2010; 12(3): 224–236. https://doi.org/10.1016/j.cmet.2010.06.009

25. Tao R, Xiong X, Depinho RA, et al. Hepatic SREBP-2 and cholesterol biosynthesis are regulated by FoxO3 and Sirt6. J Lipid Res. 2013; 54(10): 2745–2753. https://doi.org/10.1194/jlr.M039339

26. Elhanati S, Kanfi Y, Varvak A, et al. Multiple regulatory layers of SREBP1/2 by SIRT6. Cell Rep. 2013; 4(5): 905–912. https://doi.org/10.1016/j.celrep.2013.08.006

27. He J, Zhang G, Pang Q, et al. SIRT6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox-LDL condition. FEBS J. 2017; 284(9): 1324–1337. https://doi.org/10.1111/febs.14055

28. Sulaiman M, Matta MJ, Sunderesan NR, et al. Resveratrol, an activator of SIRT1, upregulates sarcoplasmic calcium ATPase and improves cardiac function in diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol. 2010; 298:3:H833–H843. https://doi.org/10.1152/ajpheart.00418.2009

29. Prola A, Silva JP, Guilbert A, et al. SIRT1 protects the heart from ER stress-induced cell death through eIF2a deacetylation. Cell Death Differ. 2017; 24(2): 343–356. https://doi.org/10.1038/cdd.2016.138

30. Cheng HL, Mostoslavsky R, Saito S, et al. Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice. Proc Natl Acad Sci U S A. 2003; 100(19): 10794–10799. https://doi.org/10.1073/pnas.1934713100

31. Tian K, Liu Z, Wang J, et al. Sirtuin-6 inhibits cardiac fibroblasts differentiation into myofibroblasts via inactivation of nuclear factor jB signaling. Transl Res. 2015; 165(3): 374–386. https://doi.org/10.1016/j.trsl.2014.08.008

32. Hsu CP, Zhai P, Yamamoto T, et al. Silent information regulator 1 protects the heart from ischemia/reperfusion. Circulation. 2010; 122(21): 2170–2182. https://doi.org/10.1161/CIRCULATIONAHA.110.958033

33. Cattelan A, Ceolotto G, Bova S, et al. NAD(+)-dependent SIRT1 deactivation has a key role on ischemia-reperfusioninduced apoptosis. Vasc Pharmacol. 2015; 70: 35–44. https://doi.org/10.1016/j.vph.2015.02.004

34. Wang B, Yang Q, Sun YY, et al. Resveratrol-enhanced autophagic flux ameliorates myocardial oxidative stress injury in diabetic mice. J Cell Mol Med. 2014; 18(8): 1599–1611.https://doi.org/10.1111/jcmm.12312

35. Wang XX, Wang XL, Tong MM, et al. SIRT6 protects cardiomyocytes against ischemia/reperfusion injury by augmenting FoxO3adependent antioxidant defense mechanisms. Basic Res Cardiol. 2016; 111(2): 13. https://doi.org/10.1007/s00395-016-0531-z

36. Maksin-Matveev A, Kanfi Y, Hochhauser E, et al. Sirtuin 6 protects the heart from hypoxic damage. Exp Cell Res. 2015; 330(1): 81–90. https://doi.org/10.1016/j.yexcr.2014.07.013

37. Mao Z, Hine C, Tian X, et al. SIRT6 promotes DNA repair under stress by activating PARP1. Science. 2011; 332:6036:1443–1446. https://doi.org/10.1126/science.1202723

38. Cheng MY, Cheng YW, Yan J, et al. SIRT6 suppresses mitochondrial defects and cell death via the NF-jB pathway in myocardial hypoxia/reoxygenation induced injury. Am J Transl Res. 2016; 8(11): 5005–5015. PMID: 27904701

39. Oka S, Alcendor R, Zhai P, et al. PPARa–Sirt1 complex mediates cardiac hypertrophy and failure through suppression of the ERR transcrip-tional pathway. Cell Metab. 2011; 14(5): 598–611. https://doi.org/10.1016/j.cmet.2011.10.001

40. Cai Y, Yu SS, Chen SR, et al. Nmnat2 protects cardiomyocytes from hypertrophy via activation of SIRT6. FEBS Lett. 2012; 586(6): 866–874. https://doi.org/10.1016/j.febslet.2012.02.014

41. Zhang X, Li W, Shen P, et al. STAT3 suppression is involved in the protective effect of SIRT6 against cardiomyocyte hypertrophy. J Cardiovasc Pharmacol. 2016; 68(3): 204– 214. https://doi.org/10.1097/FJC.0000000000000404

42. Vitiello M, Zullo A, Servillo L, et al. Multiple pathways of SIRT6 at the crossroads in the control of longevity, cancer, and cardiovascular diseases. Ageing Res Rev. 2017; 35: 301–311. https://doi.org/10.1016/j.arr.2016.10.008

43. Yuan Q, Chen L, Xiang DX, et al. Effect of resveratrol derivative BTM-0512 on high glucose-induced dysfunction of endothelial cells: role of SIRT1. Can J Physiol Pharmacol. 2011; 89:10:713–722. https://doi.org/10.1139/y11-069

44. Chen Y, Sun T, Wu J, et al. Icariin intervenes in cardiac inflammaging through upregulation of SIRT6 enzyme activity and inhibition of the NF-kappa B pathway. Biomed Res Int. 2015; 2015: 895976. https://doi.org/10.1155/2015/895976

45. Venkatasubramanian S, Noh RM, Daga S, et al. Cardiovascular effects of a novel SIRT1 activator, SRT2104, in otherwise healthy cigarette smokers. J Am Heart Assoc. 2013; 2: 3:e000042. https://doi.org/10.1161/JAHA.113.000042

46. Xu W, Deng YY, Yang L, et al. Metformin ameliorates the proinflammatory state in patients with carotid artery atherosclerosis through sirtuin 1 induction. Transl Res. 2015; 166:5:451–458. https://doi.org/10.1016/j.trsl.2015.06.002

47. Feng GS, Zhu CG, Li ZM, et al. Synthesis of the novel PARP-1 inhibitor AG-690/11026014 and its protective effects on angiotensin II-induced mouse cardiac remodeling. Acta Pharmacol Sin. 2017; 38:5:638–650. https://doi.org/10.1038/aps.2016.159

48. Servillo L, D’Onofrio N, and Balestrieri ML. Ergothioneine antioxidant function: from chemistry to cardiovascular therapeutic potential. J Cardiovasc Pharmacol. 2017; 69:4:183–191. https://doi.org/10.1097/FJC.0000000000000464

49. Sociali G, Magnone M, Ravera S, et al. Pharmacological Sirt6 inhibition improves glucose tolerance in a type 2 diabetes mouse model. The FASEB Journal.2017;31:7:3138-3149. https://doi.org/10.1096/fj.201601294R

50. Kane AE and Sinclair DA. Sirtuins and NAD+ in the Development and treatment of Metabolic and Cardiovascular Diseases. Circ Res.2018; 123(7):868-885. https://doi.org/10.1161/CIRCRESAHA.118.312498


Для цитирования:


Айтбаев К.А., Муркамилов И.Т., Муркамилова Ж.А., Кудайбергенова И.О., Юсупов Ф.А. Эпигенетические механизмы кардиопротекции: в фокусе – активация сиртуинов. Архивъ внутренней медицины. 2021;11(6):424-432. https://doi.org/10.20514/2226-6704-2021-11-6-424-432

For citation:


Aitbaev K.A., Murkamilov I.T., Murkamilova Z.A., Kudaibergenova I.O., Yusupov F.A. Epigenetic Mechanisms of Cardioprotection: Focus is on Activation of Sirtuins. The Russian Archives of Internal Medicine. 2021;11(6):424-432. https://doi.org/10.20514/2226-6704-2021-11-6-424-432

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ISSN 2226-6704 (Print)
ISSN 2411-6564 (Online)