russjcardiolРоссийский кардиологический журналRussian Journal of Cardiology1560-40712618-7620«SILICEA-POLIGRAF» LLC10.15829/1560-4071-2014-6-77-84russjcardiol-104Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEWТЕЛОМЕРЫ И АРТЕРИАЛЬНАЯ ГИПЕРТОНИЯ: ПАТОФИЗИОЛОГИЯ И КЛИНИЧЕСКИЕ ПЕРСПЕКТИВЫTELOMERES AND ARTERIAL HYPERTENSION: PATHOPHYSIOLOGY AND CLINICAL PERSPECTIVESКобалаваЖ. Д.KobalavaJ. D.

д. м.н., профессор, зав.кафедрой пропедевтики внутренних болезней медицинского факультета РУДН, зав. кафедрой внутренних болезней, кардиологии и клинической фармакологии ФПК МР РУДН

КотовскаяЮ. В.KotovskayaYu. V.

д. м.н., профессор кафедры пропедевтики внутренних болезней медицинского факультета РУДН, профессор кафедры внутренних болезней, кардиологии и клинической фармакологии ФПК МР РУДН

kotovskaya@bk.ruФПК МР Российский университет дружбы народов, Москва, РоссияРоссияPeoples' Friendship University of Russia, Moscow, Russian Federation.Russian Federation201428062014067784Copyright © Кобалава Ж.Д., Котовская Ю.В., 20142014Кобалава Ж.Д., Котовская Ю.В.Kobalava J.D., Kotovskaya Y.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://russjcardiol.elpub.ru/jour/article/view/104

Старение — основной фактор риска артериальной гипертонии (АГ) и сердечно-сосудистых заболеваний. Естественное старение при нормальном АД сопровождается параллельными структурными и функциональными изменениями в крупных артериях (ригидность), миокарде (гипертрофия) и процессах расслабления и наполнения сердечной мышцы (диастолическая дисфункция). При АГ эти изменения начинаются раньше, прогрессируют с возрастом быстрее, наблюдаются при старении с нормальным давлением и при АГ в любом возрасте. Длина теломер — особых концевых структур хромосом соматических клеток — зависит от возраста и укорачивается по мере старения. Данный обзор посвящен современным представлениям о роли теломер как биологических индикаторов старения для понимания патофизиологии эссенциальной АГ как синдрома ускоренного старения сердечно-сосудистой системы.

 

 

 

 

 

 

The ageing is the main risk factor for arterial hypertension (AH) and cardiovascular diseases. Natural ageing with normal BP is followed by changes in large arteries (rigidity), myocardium (hypertrophy) and diastolic relaxation and filling of cardiac muscle (diastolic dysfunstion). In AH these changes develop earlier and progress faster. These can be found at any age in AH. The telomere length (TL) — a special terminal structures on somatic cells chromosomes — is dependent on the age and is being shortened with age. This review concerns modern views on the role of telomeres as biological markers of ageing to understand the pathophysiology of essential arterial hypertension as a syndrome of accelerated cardiovascular system ageing.

артериальная гипертониятеломерыускоренное сердечно-сосудистое старениеarterial hypertensiontelomeresaccelerated cardiovascular ageingReferencesBlackburn EH. Switching and signaling at the telomere. Cell 2001; 106: 661-73.Blackburn EH. Switching and signaling at the telomere. Cell 2001; 106: 661-73.Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet 2005; 6: 611-22.Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet 2005; 6: 611-22.Hiyama K, Hirai Y Kyoizumi S, et al. Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol 1995; 155: 3711-5.Hiyama K, Hirai Y Kyoizumi S, et al. Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol 1995; 155: 3711-5.Chiu CP, Dragowska W, Kim NW, et al. Differential expression of telomerase activity in hematopoietic progenitorsfrom adult human bone marrow. Stem Cells 1996; 14: 239-48.Chiu CP, Dragowska W, Kim NW, et al. Differential expression of telomerase activity in hematopoietic progenitorsfrom adult human bone marrow. Stem Cells 1996; 14: 239-48.Liu K, Schoonmaker MM, Levine BL, et al. Constitutive and regulated expression of telomerase reverse transcriptase (hTERT) in human lymphocytes. Proc Natl Acad Sci U S A 1999;96:5147-52.Liu K, Schoonmaker MM, Levine BL, et al. Constitutive and regulated expression of telomerase reverse transcriptase (hTERT) in human lymphocytes. Proc Natl Acad Sci U S A 1999;96:5147-52.Harrington L, Robinson MO. Telomere dysfunction: multiple paths to the same end. Oncogene 2002; 21: 592-7.Harrington L, Robinson MO. Telomere dysfunction: multiple paths to the same end. Oncogene 2002; 21: 592-7.Artandi SE, Attardi LD. Pathways connecting telomeres and p53 in senescence, apoptosis, and cancer. Biochem Biophys Res Commun 2005; 331: 881-90.Artandi SE, Attardi LD. Pathways connecting telomeres and p53 in senescence, apoptosis, and cancer. Biochem Biophys Res Commun 2005; 331: 881-90.Coviello-McLaughlin GM, Prowse KR. Telomere length regulation during postnatal development and ageing in Mus spretus. Nucl Acids Res 1997; 25: 3051-8.Coviello-McLaughlin GM, Prowse KR. Telomere length regulation during postnatal development and ageing in Mus spretus. Nucl Acids Res 1997; 25: 3051-8.Prowse KR, Greider CW. Developmental and tissue-specific regulation of mouse telomerase and telomere length. Proc Natl Acad Sci U S A 1995; 92: 4818-22.Prowse KR, Greider CW. Developmental and tissue-specific regulation of mouse telomerase and telomere length. Proc Natl Acad Sci U S A 1995; 92: 4818-22.Okuda K, Bardeguez A, Gardner JP, et al. Telomere length in the newborn. Pediatr Res 2002; 52: 377-81.Okuda K, Bardeguez A, Gardner JP, et al. Telomere length in the newborn. Pediatr Res 2002; 52: 377-81.Slagboom PE, Droog S, Boomsma DI. Genetic determination of telomere size in humans: a twin study of three age groups. Am J Hum Genet 1994;55: 876-82.Slagboom PE, Droog S, Boomsma DI. Genetic determination of telomere size in humans: a twin study of three age groups. Am J Hum Genet 1994;55: 876-82.Friedrich U, Griese E, Schwab M, et al.Telomere length in different tissues of elderly patients. Mech Ageing Dev 2000; 119: 89-99.Friedrich U, Griese E, Schwab M, et al.Telomere length in different tissues of elderly patients. Mech Ageing Dev 2000; 119: 89-99.Jeanclos E, Schork NJ, Kyvik KO, et al.Telomere length inversely correlates with pulse pressure and is highly familial. Hypertension 2000; 36: 195-200.Jeanclos E, Schork NJ, Kyvik KO, et al.Telomere length inversely correlates with pulse pressure and is highly familial. Hypertension 2000; 36: 195-200.Takubo K, Izumiyama-Shimomura N, Honma N, et al. Telomere lengths are characteristic in each human individual. Exp Gerontol 2002; 37: 523-31.Takubo K, Izumiyama-Shimomura N, Honma N, et al. Telomere lengths are characteristic in each human individual. Exp Gerontol 2002; 37: 523-31.Nawrot TS, Staessen JA, Gardner JP, et al. Telomere length and possible link to X chromosome. Lancet 2004; 363: 507-10.Nawrot TS, Staessen JA, Gardner JP, et al. Telomere length and possible link to X chromosome. Lancet 2004; 363: 507-10.Fuster JJ, Andres V. Telomere biology and cardiovascular disease. Circ Res 2006; 99: 1167-180.Fuster JJ, Andres V. Telomere biology and cardiovascular disease. Circ Res 2006; 99: 1167-180.Leri A, Malhotra A, Liew CC, et al. Telomerase activity in rat cardiac myocytes is age and gender dependent. J Mol Cell Cardiol 2000; 32: 385-90.Leri A, Malhotra A, Liew CC, et al. Telomerase activity in rat cardiac myocytes is age and gender dependent. J Mol Cell Cardiol 2000; 32: 385-90.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: 381-5.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: 381-5.Cherif H, Tarry JL, Ozanne SE, et al. Ageing and telomeres: a study into organ- and gender- specific telomere shortening. Nucl Acids Res 2003; 31: 1576-83.Cherif H, Tarry JL, Ozanne SE, et al. Ageing and telomeres: a study into organ- and gender- specific telomere shortening. Nucl Acids Res 2003; 31: 1576-83.Kyo S, Takakura M, Kanaya T, et al. Estrogen activates telomerase. Cancer Res 1999; 59: 5917-21.Kyo S, Takakura M, Kanaya T, et al. Estrogen activates telomerase. Cancer Res 1999; 59: 5917-21.Imanishi T, Hano T, Nishio I. Estrogen reduces endothelial progenitor cell senescence through augmentation of telomerase activity. J Hypertens 2005; 23: 1699-706.Imanishi T, Hano T, Nishio I. Estrogen reduces endothelial progenitor cell senescence through augmentation of telomerase activity. J Hypertens 2005; 23: 1699-706.Blasco MA, Lee HW, Hande MP, et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 1997; 91: 25-34.Blasco MA, Lee HW, Hande MP, et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 1997; 91: 25-34.Lee HW, Blasco MA, Gottlieb GJ, et al. Essential role of mouse telomerase in highly proliferative organs. Nature 1998; 392: 569-74.Lee HW, Blasco MA, Gottlieb GJ, et al. Essential role of mouse telomerase in highly proliferative organs. Nature 1998; 392: 569-74.Rudolph KL, Chang S, Lee HW, et al. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 1999; 96: 701-12.Rudolph KL, Chang S, Lee HW, et al. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 1999; 96: 701-12.Herrera E, Samper E, Martin-Caballero J, et al. Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO J 1999; 18: 2950-60.Herrera E, Samper E, Martin-Caballero J, et al. Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO J 1999; 18: 2950-60.Franco S, Segura I, Riese HH, et al.Decreased B16F10 melanoma growth and impaired vascularization in telomerase-deficient mice with critically short telomeres. Cancer Res 2002;62: 552-9.Franco S, Segura I, Riese HH, et al.Decreased B16F10 melanoma growth and impaired vascularization in telomerase-deficient mice with critically short telomeres. Cancer Res 2002;62: 552-9.Leri A, Franco S, Zacheo A, et al. Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure associated with p53 upregulation. EMBO J 2003; 22: 131-9.Leri A, Franco S, Zacheo A, et al. Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure associated with p53 upregulation. EMBO J 2003; 22: 131-9.Wong KK, Maser RS, Bachoo RM, et al. Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature 2003; 421: 643-8.Wong KK, Maser RS, Bachoo RM, et al. Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature 2003; 421: 643-8.Perez-Rivero G, Ruiz-Torres MP, Rivas-Elena JV, et al. Mice deficient in telomerase activity develop hypertension because of an excess of endothelin production. Circulation 2006; 114: 309-17.Perez-Rivero G, Ruiz-Torres MP, Rivas-Elena JV, et al. Mice deficient in telomerase activity develop hypertension because of an excess of endothelin production. Circulation 2006; 114: 309-17.Vulliamy T, Marrone A, Goldman F, et al. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 2001; 413: 432-5.Vulliamy T, Marrone A, Goldman F, et al. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 2001; 413: 432-5.Chang S, Multani AS, Cabrera NG, et al. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet 2004; 36: 877-82.Chang S, Multani AS, Cabrera NG, et al. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet 2004; 36: 877-82.Metcalfe JA, Parkhill J, Campbell L, et al. Accelerated telomere shortening in ataxia telangiectasia. Nat Genet 1996; 13: 350-3.Metcalfe JA, Parkhill J, Campbell L, et al. Accelerated telomere shortening in ataxia telangiectasia. Nat Genet 1996; 13: 350-3.Wong JM, Collins K. Telomerase RNA level limits telomere maintenance in X-linked dyskeratosis congenita. Genes Dev 2006; 20: 2848-58.Wong JM, Collins K. Telomerase RNA level limits telomere maintenance in X-linked dyskeratosis congenita. Genes Dev 2006; 20: 2848-58.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: 325-30.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: 325-30.Sowers JR, Frohlich ED. Insulin and insulin resistance: impact on blood pressure and cardiovascular disease. Med Clin North Am 2004; 88: 63-82.Sowers JR, Frohlich ED. Insulin and insulin resistance: impact on blood pressure and cardiovascular disease. Med Clin North Am 2004; 88: 63-82.Saad MF, Rewers M, Selby J, et al. Insulin resistance and hypertension: the Insulin Resistance Atherosclerosis Study. Hypertension 2004; 43: 1324-31.Saad MF, Rewers M, Selby J, et al. Insulin resistance and hypertension: the Insulin Resistance Atherosclerosis Study. Hypertension 2004; 43: 1324-31.Fitzpatrick AL, Kronmal RA, Gardner JP, et al. Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. Am J Epidemiol 2007; 165: 14-21.Fitzpatrick AL, Kronmal RA, Gardner JP, et al. Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. Am J Epidemiol 2007; 165: 14-21.Aviv A, Valdes AM, Spector TD. Human telomere biology: pitfalls of moving fromthe laboratory to epidemiology. Int J Epidemiol 2006; 35: 1424-9.Aviv A, Valdes AM, Spector TD. Human telomere biology: pitfalls of moving fromthe laboratory to epidemiology. Int J Epidemiol 2006; 35: 1424-9.Chang E, Harley CB. Telomere length and replicative aging in human vascular tissues. Proc Natl Acad Sci U S A 1995; 92: 11190-4.Chang E, Harley CB. Telomere length and replicative aging in human vascular tissues. Proc Natl Acad Sci U S A 1995; 92: 11190-4.Okuda K, Khan MY, Skurnick J, et al. Telomere attrition of the human abdominal aorta: relationships with age and atherosclerosis. Atherosclerosis 2000; 152: 391-8.Okuda K, Khan MY, Skurnick J, et al. Telomere attrition of the human abdominal aorta: relationships with age and atherosclerosis. Atherosclerosis 2000; 152: 391-8.Cao Y Li H, Mu F-T, et al. Telomerase activation causes vascular smooth muscle cell proliferation in genetic hypertension. FASEB J 2002; 16: 96-8.Cao Y Li H, Mu F-T, et al. Telomerase activation causes vascular smooth muscle cell proliferation in genetic hypertension. FASEB J 2002; 16: 96-8.Imanishi T, Moriwaki C, Hano T, et al. Endothelial progenitor cell senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension. J Hypertens 2005; 23: 1831-7.Imanishi T, Moriwaki C, Hano T, et al. Endothelial progenitor cell senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension. J Hypertens 2005; 23: 1831-7.Kobayashi K, Imanishi T, Akasaka T. Endothelial progenitor cell differentiation and senescence in an angiotensin II-infusion rat model. Hypertens Res 2006; 29: 449-55.Kobayashi K, Imanishi T, Akasaka T. Endothelial progenitor cell differentiation and senescence in an angiotensin II-infusion rat model. Hypertens Res 2006; 29: 449-55.Epstein M, Sowers JR. Diabetes mellitus and hypertension. Hypertension 1992; 19: 403-18.Epstein M, Sowers JR. Diabetes mellitus and hypertension. Hypertension 1992; 19: 403-18.National High Blood Pressure Education Program Working Group report on hypertension in diabetes. Hypertension 1994; 23: 145-58.National High Blood Pressure Education Program Working Group report on hypertension in diabetes. Hypertension 1994; 23: 145-58.Griendling KK, Alexander RW. Oxidative stress and cardiovascular disease. Circulation 1997;96:3593-601.Griendling KK, Alexander RW. Oxidative stress and cardiovascular disease. Circulation 1997;96:3593-601.Gress TW, Nieto FJ, Shahar E, et al. for The Atherosclerosis Risk in Communities Study. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. N Engl J Med 2000; 342: 905-12.Gress TW, Nieto FJ, Shahar E, et al. for The Atherosclerosis Risk in Communities Study. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. N Engl J Med 2000; 342: 905-12.Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004; 24: 816-23.Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004; 24: 816-23.Savoia C, Schiffrin EL. Inflammation in hypertension. Curr Opin Nephrol Hypertens 2006; 15: 152-8.Savoia C, Schiffrin EL. Inflammation in hypertension. Curr Opin Nephrol Hypertens 2006; 15: 152-8.Xu D, Neville R, Finkel T. Homocysteine accelerates endothelial cell senescence. FEBS Lett 2000; 470: 20-24.Xu D, Neville R, Finkel T. Homocysteine accelerates endothelial cell senescence. FEBS Lett 2000; 470: 20-24.Breitschopf K, Zeiher AM, Dimmeler S. Pro-atherogenic factors induce telomerase inactivation in endothelial cells through an Akt-dependent mechanism. FEBS Lett 2001; 493: 21-5.Breitschopf K, Zeiher AM, Dimmeler S. Pro-atherogenic factors induce telomerase inactivation in endothelial cells through an Akt-dependent mechanism. FEBS Lett 2001; 493: 21-5.Kurz DJ, Decary S, Hong Y et al. Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells. J Cell Sci 2004; 117: 2417-26.Kurz DJ, Decary S, Hong Y et al. Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells. J Cell Sci 2004; 117: 2417-26.Gardner JP, Li S, Srinivasan SR, et al. Rise in insulin resistance is associated with escalated telomere attrition. Circulation 2005; 111: 2171-7.Gardner JP, Li S, Srinivasan SR, et al. Rise in insulin resistance is associated with escalated telomere attrition. Circulation 2005; 111: 2171-7.Matthews C, Gorenne I, Scott S, et al. Vascular smooth muscle cells undergo telomere- based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Circ Res 2006; 99: 156-64.Matthews C, Gorenne I, Scott S, et al. Vascular smooth muscle cells undergo telomere- based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Circ Res 2006; 99: 156-64.Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol 2007; 292: C82-C97.Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol 2007; 292: C82-C97.Kunieda T, Minamino T, Nishi J, et al. Angiotensin II induces premature senescence of vascular smooth muscle cells and accelerates the development of atherosclerosis via a p21- dependent pathway. Circulation 2006; 114: 953-60.Kunieda T, Minamino T, Nishi J, et al. Angiotensin II induces premature senescence of vascular smooth muscle cells and accelerates the development of atherosclerosis via a p21- dependent pathway. Circulation 2006; 114: 953-60.Benetos A, Gardner JP, Kimura M, et al. Aldosterone and telomere length in white blood cells. J Gerontol A Biol Sci Med Sci 2005; 60: 1593-6.Benetos A, Gardner JP, Kimura M, et al. Aldosterone and telomere length in white blood cells. J Gerontol A Biol Sci Med Sci 2005; 60: 1593-6.Lim PO, Struthers AD, MacDonald TM. The neurohormonal natural history of essential hypertension: towards primary or tertiary aldosteronism? J Hypertens 2002; 20: 11-5.Lim PO, Struthers AD, MacDonald TM. The neurohormonal natural history of essential hypertension: towards primary or tertiary aldosteronism? J Hypertens 2002; 20: 11-5.Minamino T, Miyauchi H, Yoshida T, et al. Endothelial cell senescence in human atherosclerosis. Role of telomere in endothelial dysfunction. Circulation 2002; 105: 1541-4.Minamino T, Miyauchi H, Yoshida T, et al. Endothelial cell senescence in human atherosclerosis. Role of telomere in endothelial dysfunction. Circulation 2002; 105: 1541-4.Benetos A, Gardner JP, Zureik M, et al. Short telomeres are associated with increased carotid atherosclerosis in hypertensive subjects. Hypertension 2004; 43: 182-5.Benetos A, Gardner JP, Zureik M, et al. Short telomeres are associated with increased carotid atherosclerosis in hypertensive subjects. Hypertension 2004; 43: 182-5.Chimenti C, Kajstura J, Torella D, et al. Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure. Circ Res 2003; 93: 604-13.Chimenti C, Kajstura J, Torella D, et al. Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure. Circ Res 2003; 93: 604-13.Oh H, Wang SC, Prahash A, et al. Telomere attrition and Chk2 activation in human heart failure. Proc Natl Acac Sci U S A 2003; 100: 5378-83.Oh H, Wang SC, Prahash A, et al. Telomere attrition and Chk2 activation in human heart failure. Proc Natl Acac Sci U S A 2003; 100: 5378-83.Urbanek K, Quaini F, Tasca G, et al. Intense myocyte formation from cardiac stem cells in human cardiac ypertrophy. Proc Natl Acad Sci U S A 2003; 100: 10440-5.Urbanek K, Quaini F, Tasca G, et al. Intense myocyte formation from cardiac stem cells in human cardiac ypertrophy. Proc Natl Acad Sci U S A 2003; 100: 10440-5.Takimoto E, Kass DA. Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension 2007; 49: 241-8.Takimoto E, Kass DA. Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension 2007; 49: 241-8.Hamet P, Thorin-Trescases N, Moreau P, et al. Workshop: excess growth and apoptosis: is hypertension a case of accelerated aging of cardiovascular cells? Hypertension 2001; 37: 760-6.Hamet P, Thorin-Trescases N, Moreau P, et al. Workshop: excess growth and apoptosis: is hypertension a case of accelerated aging of cardiovascular cells? Hypertension 2001; 37: 760-6.Gonzalez A, Ravassa S, Lopez B, et al. Apoptosis in hypertensive heart disease: a clinical approach. Curr Opin Cardiol 2006; 21: 288-94.Gonzalez A, Ravassa S, Lopez B, et al. Apoptosis in hypertensive heart disease: a clinical approach. Curr Opin Cardiol 2006; 21: 288-94.Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003; 114: 763-76.Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003; 114: 763-76.Oh H, Bradfute SB, Gallardo TD, et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci U S A 2003; 100: 12313-8.Oh H, Bradfute SB, Gallardo TD, et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci U S A 2003; 100: 12313-8.Urbanek K, Torella D, Sheikh F, et al. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci U S A 2005; 102: 8692-7.Urbanek K, Torella D, Sheikh F, et al. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci U S A 2005; 102: 8692-7.Oh H, Taffet GE, Youker KA, et al. Telomerase reverse transcriptase promotes cardiac muscle cell proliferation, hypertrophy, and survival. Proc Natl Acad Sci U S A 2001; 98: 10308-13.Oh H, Taffet GE, Youker KA, et al. Telomerase reverse transcriptase promotes cardiac muscle cell proliferation, hypertrophy, and survival. Proc Natl Acad Sci U S A 2001; 98: 10308-13.Dhalla AK, Hill MF, Singal PK. Role of oxidative stress in transition of hypertrophy to heart failure. J Am Coll Cardiol 1996; 28: 506-14.Dhalla AK, Hill MF, Singal PK. Role of oxidative stress in transition of hypertrophy to heart failure. J Am Coll Cardiol 1996; 28: 506-14.Rota M, LeCapitaine N, Hosoda T, et al. Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66Shc gene. Circ Res 2006; 99: 42-52.Rota M, LeCapitaine N, Hosoda T, et al. Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66Shc gene. Circ Res 2006; 99: 42-52.Migliaccio E, Giorgio M, Mele S, et al. The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 1999; 402: 309-13.Migliaccio E, Giorgio M, Mele S, et al. The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 1999; 402: 309-13.Giorgio M, Migliaccio E, Orsini F, et al. Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell 2005; 122: 221-33.Giorgio M, Migliaccio E, Orsini F, et al. Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell 2005; 122: 221-33.Buemi M, Nostro L, Aloisi C, et al. Kidney aging: from phenotype to genetics. Rejuvenation Res 2005; 8: 101-9.Buemi M, Nostro L, Aloisi C, et al. Kidney aging: from phenotype to genetics. Rejuvenation Res 2005; 8: 101-9.Melk A, Ramassar V, Helms LM, et al. Telomere shortening in kidneys with age. J Am Soc Nephrol 2000; 11: 444-53.Melk A, Ramassar V, Helms LM, et al. Telomere shortening in kidneys with age. J Am Soc Nephrol 2000; 11: 444-53.Thorin-Trescases N, deBlois D, Hamet P. Evidence of an altered in vivo vascular cell turnover in spontaneously hypertensive rats and its modulation by long-term antihypertensive treatment. J Cardiovasc Pharmacol 2001; 38: 764-74.Thorin-Trescases N, deBlois D, Hamet P. Evidence of an altered in vivo vascular cell turnover in spontaneously hypertensive rats and its modulation by long-term antihypertensive treatment. J Cardiovasc Pharmacol 2001; 38: 764-74.Rosario RF, Wesson DE. Primary hypertension and nephropathy. Curr Opin Nephrol Hypertens 2006; 15: 130-4.Rosario RF, Wesson DE. Primary hypertension and nephropathy. Curr Opin Nephrol Hypertens 2006; 15: 130-4.Ono H, Ono Y Nephrosclerosis and hypertension. Med Clin North Am 1997; 81: 1273-88.Ono H, Ono Y Nephrosclerosis and hypertension. Med Clin North Am 1997; 81: 1273-88.Samani NJ, Boultby R, Butler R, et al. Telomere shortening in atherosclerosis. Lancet 2001;358: 472-3.Samani NJ, Boultby R, Butler R, et al. Telomere shortening in atherosclerosis. Lancet 2001;358: 472-3.Marx N, Wohrle J, Nusser T, et al. Pioglitazone reduces neointima volume after coronary stent implantation: a randomized, placebo-controlled, double-blind trial in nondiabetic patients. Circulation 2005; 112: 2792-8.Marx N, Wohrle J, Nusser T, et al. Pioglitazone reduces neointima volume after coronary stent implantation: a randomized, placebo-controlled, double-blind trial in nondiabetic patients. Circulation 2005; 112: 2792-8.Ogawa D, Nomiyama T, Nakamachi T, et al. Activation of peroxisome proliferator-activated receptor gamma suppresses telomerase activity in vascular smooth muscle cells. Circ Res 2006;98:e50-e59.Ogawa D, Nomiyama T, Nakamachi T, et al. Activation of peroxisome proliferator-activated receptor gamma suppresses telomerase activity in vascular smooth muscle cells. Circ Res 2006;98:e50-e59.Brouilette SW, Moore JS, McMahon AD, et al. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet 2007; 369: 107-14.Brouilette SW, Moore JS, McMahon AD, et al. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet 2007; 369: 107-14.Fuster JJ, Diez J., Andres V. Telomere dysfunction in hypertension. Journal of Hypertension 2007, 25: 2185-92.Fuster JJ, Diez J., Andres V. Telomere dysfunction in hypertension. Journal of Hypertension 2007, 25: 2185-92.

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