russjcardiolРоссийский кардиологический журналRussian Journal of Cardiology1560-40712618-7620«SILICEA-POLIGRAF» LLC10.15829/1560-4071-2016-9-84-89russjcardiol-564Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEWДЛИНА ТЕЛОМЕР И АТЕРОСКЛЕРОЗTELOMERE LENGTH AND ATHEROSCLEROSISДрапкинаО. М.DrapkinaO. M.

Доктор медицинских наук, профессор, руководитель отдела  фундаментальных и прикладных аспектов ожирения, заместитель директора по научной и лечебной работе

drapkina@bk.ruШепельР. Н.ShepelR. N.

Младший научный сотрудник  отдела  фундаментальных  и прикладных аспектов ожирения

r.n.shepel@mail.ruГосударственный научно-исследовательский центр профилактической медицины Минздрава России, МоскваРоссияNational Research Center for Preventive Medicine of the Ministry of Health, MoscowRussian Federation201628092016098489Copyright © Драпкина О.М., Шепель Р.Н., 20162016Драпкина О.М., Шепель Р.Н.Drapkina O.M., Shepel R.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://russjcardiol.elpub.ru/jour/article/view/564

Развитие и прогрессирование атеросклероза в большинстве случаев происходит на протяжении десятилетий и на ранних стадиях не всегда имеет клинические проявления. Результаты многочисленных исследований свидетельствуют о том, что длина теломер отражает суммарную степень повреждения ДНК факторами, которые ответственны за развитие атеросклероза и его осложнений. Скорость укорочения теломер увеличивается еще до начала заболевания, что может иметь диагностическое и прогностическое значение.  

The development  and progression of atherosclerosis in most cases takes decades, and at early stages does not present clinically. Multiple studies results witness that telomere   length  reflects  total  grade   of  DNA damage by  the  factors  that  are responsible for atherosclerosis and its complications. Velocity of telomeres shortening  increases even before the disease onset  that may play diagnostic  and predictive role.

атеросклерозтеломерыклеточное старениеокислительный стрессatherosclerosistelomerescellular ageingoxidative stressReferencesLusis AJ. Atherosclerosis. Nature 2000; 407:233–241.Lusis AJ. Atherosclerosis. Nature 2000; 407:233–241.Willeit P, Willeit J, Brandstatter A, Ehrlenbach S. et al. Cellular aging reflected by leukocyte telomere length predicts advanced atherosclerosis and cardiovascular disease risk. Arterioscler Thromb Vasc Biol 2010; 30:1649–1656.Willeit P, Willeit J, Brandstatter A, Ehrlenbach S. et al. Cellular aging reflected by leukocyte telomere length predicts advanced atherosclerosis and cardiovascular disease risk. Arterioscler Thromb Vasc Biol 2010; 30:1649–1656.Drapkina OM, Shepel RN. Telomeres and telomerase complex. The main clinical manifestation of genetic malfunctioning. Cardiovascular Therapy and Prevention 2015; 14(1): 70-77. Russian (Драпкина О.М., Шепель Р.Н. Теломеры и теломеразный комплекс. Основные клинические проявления генетического сбоя. Кардиоваскулярная терапия и профилактика 2015, 14(1): 70-77).Drapkina OM, Shepel RN. Telomeres and telomerase complex. The main clinical manifestation of genetic malfunctioning. Cardiovascular Therapy and Prevention 2015; 14(1): 70-77. Russian (Драпкина О.М., Шепель Р.Н. Теломеры и теломеразный комплекс. Основные клинические проявления генетического сбоя. Кардиоваскулярная терапия и профилактика 2015, 14(1): 70-77).Grabowski P, Hultdin M, Karlsson K, et al. Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status. Blood 2005; 105:4807–4812.Grabowski P, Hultdin M, Karlsson K, et al. Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status. Blood 2005; 105:4807–4812.Blackburn EH. Switching and signaling at the telomere. Cell 2001; 106(6):661-73Blackburn EH. Switching and signaling at the telomere. Cell 2001; 106(6):661-73de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 2005; 19(18):2100-2110.de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 2005; 19(18):2100-2110.Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet 2008; 42:301-34.Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet 2008; 42:301-34.De Boeck G, Forsyth RG, Praet M, Hogendoorn PC. Telomere-associated proteins: cross-talk between telomere maintenance and telomere-lengthening mechanisms. J Pathol 2009; 217:327–344.De Boeck G, Forsyth RG, Praet M, Hogendoorn PC. Telomere-associated proteins: cross-talk between telomere maintenance and telomere-lengthening mechanisms. J Pathol 2009; 217:327–344.Rose A, Patel S, Meier I. The plant nuclear envelope. Planta 2004; 218: 327—336.Rose A, Patel S, Meier I. The plant nuclear envelope. Planta 2004; 218: 327—336.Pennaneach V, Putnam C D, Kolodner RD. Chromosome healing by de novo telomere addition in Saccharomyces cerevisiae. Mol. Microbiol 2006; 59:1357—1368.Pennaneach V, Putnam C D, Kolodner RD. Chromosome healing by de novo telomere addition in Saccharomyces cerevisiae. Mol. Microbiol 2006; 59:1357—1368.Pedram M, Sprung C N, Gao Q, Reynolds G E, Murnane JP. Telomere position effect and silencing of transgenes near telomeres in the mouse. Mol. Cell. Biol 2006; 26:1865—1878.Pedram M, Sprung C N, Gao Q, Reynolds G E, Murnane JP. Telomere position effect and silencing of transgenes near telomeres in the mouse. Mol. Cell. Biol 2006; 26:1865—1878.Olovnik AI. A theory of marginotomy: the incomplete copying of template margin in enzymatic synthesis of polynucleotides and biological significance of the phenomenon. J. Theor. Biol 1973; 41:181—190.Olovnik AI. A theory of marginotomy: the incomplete copying of template margin in enzymatic synthesis of polynucleotides and biological significance of the phenomenon. J. Theor. Biol 1973; 41:181—190.Brouilette SW, Whittaker A, Stevens SE, van der Harst P, et al. Telomere length is shorter in healthy offspring of subjects with coronary artery disease: support for the telomere hypothesis. Heart 2008; 94:422–425.Brouilette SW, Whittaker A, Stevens SE, van der Harst P, et al. Telomere length is shorter in healthy offspring of subjects with coronary artery disease: support for the telomere hypothesis. Heart 2008; 94:422–425.Stewart JA, Chaiken MF, Wang F, Price CM. Maintaining the end: Role of telomere proteins in end-protection, telomere replication and length regulation. Mutat Res: Fundam Mol Mech Mutagen 2011,doi:10.1016/j.mrfmmm.2011.08.011.Stewart JA, Chaiken MF, Wang F, Price CM. Maintaining the end: Role of telomere proteins in end-protection, telomere replication and length regulation. Mutat Res: Fundam Mol Mech Mutagen 2011,doi:10.1016/j.mrfmmm.2011.08.011.Gilson E, Segal-Bendirdjian E. The telomere story or the triumph of an open-minded research. Biochimie 2010; 92:321–326.Gilson E, Segal-Bendirdjian E. The telomere story or the triumph of an open-minded research. Biochimie 2010; 92:321–326.Von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci 2002; 27:339–344.Von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci 2002; 27:339–344.De Meyer T, Rietzschel ER, De Buyzere ML, et al. Systemic telomere length and preclinical atherosclerosis: the Asklepios Study. Eur Heart J 2009; 30:3074–3081.De Meyer T, Rietzschel ER, De Buyzere ML, et al. Systemic telomere length and preclinical atherosclerosis: the Asklepios Study. Eur Heart J 2009; 30:3074–3081.Kawanishi S, Oikawa S. Mechanism of telomere shortening by oxidative stress. Ann NY Acad Sci 2004; 1019:278–284.Kawanishi S, Oikawa S. Mechanism of telomere shortening by oxidative stress. Ann NY Acad Sci 2004; 1019:278–284.Cai H, Harrison DG. Endothelial dysfunction in cardiovascular disease: the role of oxidant stress. Circ Res 2000; 87:840–844Cai H, Harrison DG. Endothelial dysfunction in cardiovascular disease: the role of oxidant stress. Circ Res 2000; 87:840–844Burke A, Fitzgerald GA. Oxidative stress and smoking-induced vascular injury. Prog Cardiovasc Dis 2003; 46:79–90.Burke A, Fitzgerald GA. Oxidative stress and smoking-induced vascular injury. Prog Cardiovasc Dis 2003; 46:79–90.Valdes AM, Andrew T, Gardner JP, et al. Obesity, cigarette smoking,and telomere length in women. Lancet 2005; 366:662 – 664.Valdes AM, Andrew T, Gardner JP, et al. Obesity, cigarette smoking,and telomere length in women. Lancet 2005; 366:662 – 664.Morla M, Busquets X, Pons J, Sauleda J, MacNee W, Agusti AG.Telomere shortening in smokers with and without COPD. Eur Respir J 2006; 27:525 – 528.Morla M, Busquets X, Pons J, Sauleda J, MacNee W, Agusti AG.Telomere shortening in smokers with and without COPD. Eur Respir J 2006; 27:525 – 528.J. Huzen, L. S. M. Wong, D. J. van Veldhuisen, N. J. Samanib et al. Telomere length loss due to smoking and metabolic traits. Journal of Internal Medicine 2014; 275(2):155-163.J. Huzen, L. S. M. Wong, D. J. van Veldhuisen, N. J. Samanib et al. Telomere length loss due to smoking and metabolic traits. Journal of Internal Medicine 2014; 275(2):155-163.Drapkina O.M., Shepel R.N. The modern conception of the proper role of telomeres and telomerase in pathogenesis of hypertension. Arterial hypertension 2013; 19(4):290-298. Russian (Драпкина О.М., Шепель Р.Н. Современные представления о роли теломер и теломеразы в патогенезе гипертонической болезни. Артериальная гипертензия 2013, 19(4):290-298.)Drapkina O.M., Shepel R.N. The modern conception of the proper role of telomeres and telomerase in pathogenesis of hypertension. Arterial hypertension 2013; 19(4):290-298. Russian (Драпкина О.М., Шепель Р.Н. Современные представления о роли теломер и теломеразы в патогенезе гипертонической болезни. Артериальная гипертензия 2013, 19(4):290-298.)Jeanclos E, Schork NJ, Kyvik KO, Kimura M, Skurnick JH, Aviv A.Telomere length inversely correlates with pulse pressure and is highly familial. Hypertension 2000; 36:195–200.Jeanclos E, Schork NJ, Kyvik KO, Kimura M, Skurnick JH, Aviv A.Telomere length inversely correlates with pulse pressure and is highly familial. Hypertension 2000; 36:195–200.Benetos A, Okuda K, Lajemi M, et al. Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity. Hypertension 2001; 37:381-385.Benetos A, Okuda K, Lajemi M, et al. Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity. Hypertension 2001; 37:381-385.Ronti T, Lupattelli G, Mannarino E. The endocrine function of adipose tissue. Clin Endocrinol 2006; 64(4):355–365.Ronti T, Lupattelli G, Mannarino E. The endocrine function of adipose tissue. Clin Endocrinol 2006; 64(4):355–365.Gardner JP, Shengxu L, Srinivasan SR, Wei C, et al. Rise in insulin resistance is associated with escalated telomere attrition. Circulation 2005; 111:2171–2177.Gardner JP, Shengxu L, Srinivasan SR, Wei C, et al. Rise in insulin resistance is associated with escalated telomere attrition. Circulation 2005; 111:2171–2177.Su Y, Liu XM, Sun YM, et al. The relationship between endothelial dysfunction and oxidative stress in diabetes and pre-diabetes. Int J Clin Pract 2008; 62:877–882.Su Y, Liu XM, Sun YM, et al. The relationship between endothelial dysfunction and oxidative stress in diabetes and pre-diabetes. Int J Clin Pract 2008; 62:877–882.Brodsky SV, Gealekman O, Chen J, Zhang F, et al. Prevention and reversal of premature endothelial cell senescence and vasculopathy in obesity-induced diabetes by ebselen. Circ Res 2004; 94:377–384.Brodsky SV, Gealekman O, Chen J, Zhang F, et al. Prevention and reversal of premature endothelial cell senescence and vasculopathy in obesity-induced diabetes by ebselen. Circ Res 2004; 94:377–384.Adaikalakoteswari A, Balasubramanyam M, Mohan V. Telomere shortening occurs in Asian Indian Type 2 diabetic patients. Diabet Med 2005; 22:1151–1156.Adaikalakoteswari A, Balasubramanyam M, Mohan V. Telomere shortening occurs in Asian Indian Type 2 diabetic patients. Diabet Med 2005; 22:1151–1156.Zee RL, Castonguay AJ, Barton NS, Germer S, Martin M. Mean leucocyte telomere length shortening and type 2 diabetes mellitus : a case-control study. Translational Res 2010; 155:166–169.Zee RL, Castonguay AJ, Barton NS, Germer S, Martin M. Mean leucocyte telomere length shortening and type 2 diabetes mellitus : a case-control study. Translational Res 2010; 155:166–169.Salpea KD, Talmud PJ, Cooper JA, Maubaret CG, Stephens JW, Abelak K, Humphries SE. Association of telomere length with type 2 diabetes, oxidative stress and UCP2 gene variation. Atherosclerosis. 2010; 209:42–50.Salpea KD, Talmud PJ, Cooper JA, Maubaret CG, Stephens JW, Abelak K, Humphries SE. Association of telomere length with type 2 diabetes, oxidative stress and UCP2 gene variation. Atherosclerosis. 2010; 209:42–50.Olivieri F, Lorenzi M, Antonicelli R, et al. Leukocyte telomere shortening in elderly Type2DM patients with previous myocardial infarction. Atherosclerosis 2009; 206(2): 588-593.Olivieri F, Lorenzi M, Antonicelli R, et al. Leukocyte telomere shortening in elderly Type2DM patients with previous myocardial infarction. Atherosclerosis 2009; 206(2): 588-593.Fyhrquist F, Tiitu A, Saijonmaa O, et al. Telomere Length and progression of diabetic nephropathy in patients with type 1 diabetes. J Intern Med 2010; 267(3):278-286.Fyhrquist F, Tiitu A, Saijonmaa O, et al. Telomere Length and progression of diabetic nephropathy in patients with type 1 diabetes. J Intern Med 2010; 267(3):278-286.Tentolouris N, Nzietchueng R, Cattan V, et al. (2007). White blood cells Telomere Length is shorter in males with type 2 diabetes and microalbuminuria. Diabetes Care 2007; 30(11):2909-2915.Tentolouris N, Nzietchueng R, Cattan V, et al. (2007). White blood cells Telomere Length is shorter in males with type 2 diabetes and microalbuminuria. Diabetes Care 2007; 30(11):2909-2915.Adaikalakoteswari A, Balasubramanyam M, Ravikumar R, Deepa R, Mohan V. Association of telomere shortening with impaired glucose tolerance and diabetic macroangiopathy. Atherosclerosis 2007; 195: 83–89.Adaikalakoteswari A, Balasubramanyam M, Ravikumar R, Deepa R, Mohan V. Association of telomere shortening with impaired glucose tolerance and diabetic macroangiopathy. Atherosclerosis 2007; 195: 83–89.Demissie S, Levy D, Benjamin EJ. et al. Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study. Aging Cell 2006; 5:325–330.Demissie S, Levy D, Benjamin EJ. et al. Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study. Aging Cell 2006; 5:325–330.Al-Attas O, Al-Daghri N, Bamakhramah A, et al. Telomere length in relation to insulin resistance, inflammation and obesity among Arab youth. Acta Paediatr 2010; 99:896–899.Al-Attas O, Al-Daghri N, Bamakhramah A, et al. Telomere length in relation to insulin resistance, inflammation and obesity among Arab youth. Acta Paediatr 2010; 99:896–899.Daubenmiera J, Linb J, Blackburnb E, Hechta F. Changes in stress, eating, and metabolic factors are related to changes in telomerase activity in a randomized mindfulness intervention pilot study. Psychoneuroendocrinology 2012; 37(7): 917–928.Daubenmiera J, Linb J, Blackburnb E, Hechta F. Changes in stress, eating, and metabolic factors are related to changes in telomerase activity in a randomized mindfulness intervention pilot study. Psychoneuroendocrinology 2012; 37(7): 917–928.Zhu H, Belcher M, van der Harst P. Healthy aging and disease: role for telomere biology? Clin Sci 2011; 120:427–440.Zhu H, Belcher M, van der Harst P. Healthy aging and disease: role for telomere biology? Clin Sci 2011; 120:427–440.Drapkina O.M., Shepel R.N. Low sodium diet: pros and cons. Ration Pharmacother Cardiol 2015; 11(2):190-195. Russian (Драпкина О.М., Шепель Р.Н. Диета с низким содержанием поваренной соли: за и против. Рациональная фармакотерапия в кардиологии 2015, 11(2):190-195).Drapkina O.M., Shepel R.N. Low sodium diet: pros and cons. Ration Pharmacother Cardiol 2015; 11(2):190-195. Russian (Драпкина О.М., Шепель Р.Н. Диета с низким содержанием поваренной соли: за и против. Рациональная фармакотерапия в кардиологии 2015, 11(2):190-195).Cherkas LF, Hunkin JL, Kato BS, Richards J B, Gardner JP, Surdulescu GL, I Aviv A. The association between physical activity in leisure time and leukocyte telomere length. Archives of Internal Medicine 2008; 168:154-158.Cherkas LF, Hunkin JL, Kato BS, Richards J B, Gardner JP, Surdulescu GL, I Aviv A. The association between physical activity in leisure time and leukocyte telomere length. Archives of Internal Medicine 2008; 168:154-158.Krauss J, Farzaneh-Far R, Puterman E, Na B, Lin J, et al. Physical Fitness and Telomere Length in Patients with Coronary Heart Disease: Findings from the Heart and Soul Study. PLoS ONE 2011; 6(11): e26983. oi:10.1371/journal.pone.0026983Krauss J, Farzaneh-Far R, Puterman E, Na B, Lin J, et al. Physical Fitness and Telomere Length in Patients with Coronary Heart Disease: Findings from the Heart and Soul Study. PLoS ONE 2011; 6(11): e26983. oi:10.1371/journal.pone.0026983Denham J, Nelson CP, O’Brien BJ, Nankervis SA, Denniff M, et al. Longer Leukocyte Telomeres Are Аssociated with Ultra-Endurance Exercise Independent of Cardiovascular Risk Factors. PLoS ONE 2013; 8(7): e69377. doi:10.1371/journal.pone.0069377Denham J, Nelson CP, O’Brien BJ, Nankervis SA, Denniff M, et al. Longer Leukocyte Telomeres Are Аssociated with Ultra-Endurance Exercise Independent of Cardiovascular Risk Factors. PLoS ONE 2013; 8(7): e69377. doi:10.1371/journal.pone.0069377Farzaneh – Far R., Lin J., E.pel E.S., Harris W.S., Blackburn E.H., Whooley M.A. Association of marine omega – 3 fatty acid levels with telomeric aging in patients with coronary heart disease. JAMA 2010; 303: 250–257.Farzaneh – Far R., Lin J., E.pel E.S., Harris W.S., Blackburn E.H., Whooley M.A. Association of marine omega – 3 fatty acid levels with telomeric aging in patients with coronary heart disease. JAMA 2010; 303: 250–257.Bode-Boger SM, Martens-Lobenhoffer J, Tager M, Schroder H, Scalera F. Aspirin reduces endothelial cell senescence. Biochem Biophys Res Commun 2005; 334:1226–1232.Bode-Boger SM, Martens-Lobenhoffer J, Tager M, Schroder H, Scalera F. Aspirin reduces endothelial cell senescence. Biochem Biophys Res Commun 2005; 334:1226–1232.Donnini S, Terzuoli E, Ziche M, Morbidelli L. Sulfhydryl angiotensinconverting enzyme inhibitor promotes endothelial cell survival through nitric-oxide synthase, fibroblast growth factor-2, and telomerase crosstalk. J Pharmacol Exp Ther 2010; 332 (3):776–784.Donnini S, Terzuoli E, Ziche M, Morbidelli L. Sulfhydryl angiotensinconverting enzyme inhibitor promotes endothelial cell survival through nitric-oxide synthase, fibroblast growth factor-2, and telomerase crosstalk. J Pharmacol Exp Ther 2010; 332 (3):776–784.Spyridopoulos I, Haendeler J, Urbich C, et al. Statins enhance migratory capacity by upregulation of the telomere repeat-binding factor TRF2 in endothelial progenitor cells. Circulation 2004; 110:3136–3142.Spyridopoulos I, Haendeler J, Urbich C, et al. Statins enhance migratory capacity by upregulation of the telomere repeat-binding factor TRF2 in endothelial progenitor cells. Circulation 2004; 110:3136–3142.

The authors declare that there are no conflicts of interest present.