Статья
ТЕЛОМЕРЫ И АРТЕРИАЛЬНАЯ ГИПЕРТОНИЯ: ПАТОФИЗИОЛОГИЯ И КЛИНИЧЕСКИЕ ПЕРСПЕКТИВЫ
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.
1. Blackburn EH. Switching and signaling at the telomere. Cell 2001; 106: 661-73.
2. Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet 2005; 6: 611-22.
3. Hiyama K, Hirai Y Kyoizumi S, et al. Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol 1995; 155: 3711-5.
4. 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.
5. 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.
6. Harrington L, Robinson MO. Telomere dysfunction: multiple paths to the same end. Oncogene 2002; 21: 592-7.
7. Artandi SE, Attardi LD. Pathways connecting telomeres and p53 in senescence, apoptosis, and cancer. Biochem Biophys Res Commun 2005; 331: 881-90.
8. Coviello-McLaughlin GM, Prowse KR. Telomere length regulation during postnatal development and ageing in Mus spretus. Nucl Acids Res 1997; 25: 3051-8.
9. 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.
10. Okuda K, Bardeguez A, Gardner JP, et al. Telomere length in the newborn. Pediatr Res 2002; 52: 377-81.
11. 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.
12. Friedrich U, Griese E, Schwab M, et al.Telomere length in different tissues of elderly patients. Mech Ageing Dev 2000; 119: 89-99.
13. Jeanclos E, Schork NJ, Kyvik KO, et al.Telomere length inversely correlates with pulse pressure and is highly familial. Hypertension 2000; 36: 195-200.
14. Takubo K, Izumiyama-Shimomura N, Honma N, et al. Telomere lengths are characteristic in each human individual. Exp Gerontol 2002; 37: 523-31.
15. Nawrot TS, Staessen JA, Gardner JP, et al. Telomere length and possible link to X chromosome. Lancet 2004; 363: 507-10.
16. Fuster JJ, Andres V. Telomere biology and cardiovascular disease. Circ Res 2006; 99: 1167-180.
17. 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.
18. 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.
19. 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.
20. Kyo S, Takakura M, Kanaya T, et al. Estrogen activates telomerase. Cancer Res 1999; 59: 5917-21.
21. Imanishi T, Hano T, Nishio I. Estrogen reduces endothelial progenitor cell senescence through augmentation of telomerase activity. J Hypertens 2005; 23: 1699-706.
22. Blasco MA, Lee HW, Hande MP, et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 1997; 91: 25-34.
23. Lee HW, Blasco MA, Gottlieb GJ, et al. Essential role of mouse telomerase in highly proliferative organs. Nature 1998; 392: 569-74.
24. Rudolph KL, Chang S, Lee HW, et al. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 1999; 96: 701-12.
25. 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.
26. 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.
27. 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.
28. Wong KK, Maser RS, Bachoo RM, et al. Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature 2003; 421: 643-8.
29. 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.
30. 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.
31. 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.
32. Metcalfe JA, Parkhill J, Campbell L, et al. Accelerated telomere shortening in ataxia telangiectasia. Nat Genet 1996; 13: 350-3.
33. Wong JM, Collins K. Telomerase RNA level limits telomere maintenance in X-linked dyskeratosis congenita. Genes Dev 2006; 20: 2848-58.
34. 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.
35. Sowers JR, Frohlich ED. Insulin and insulin resistance: impact on blood pressure and cardiovascular disease. Med Clin North Am 2004; 88: 63-82.
36. Saad MF, Rewers M, Selby J, et al. Insulin resistance and hypertension: the Insulin Resistance Atherosclerosis Study. Hypertension 2004; 43: 1324-31.
37. 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.
38. Aviv A, Valdes AM, Spector TD. Human telomere biology: pitfalls of moving fromthe laboratory to epidemiology. Int J Epidemiol 2006; 35: 1424-9.
39. Chang E, Harley CB. Telomere length and replicative aging in human vascular tissues. Proc Natl Acad Sci U S A 1995; 92: 11190-4.
40. 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.
41. 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.
42. 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.
43. 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.
44. Epstein M, Sowers JR. Diabetes mellitus and hypertension. Hypertension 1992; 19: 403-18.
45. National High Blood Pressure Education Program Working Group report on hypertension in diabetes. Hypertension 1994; 23: 145-58.
46. Griendling KK, Alexander RW. Oxidative stress and cardiovascular disease. Circulation 1997;96:3593-601.
47. 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.
48. 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.
49. Savoia C, Schiffrin EL. Inflammation in hypertension. Curr Opin Nephrol Hypertens 2006; 15: 152-8.
50. Xu D, Neville R, Finkel T. Homocysteine accelerates endothelial cell senescence. FEBS Lett 2000; 470: 20-24.
51. 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.
52. 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.
53. Gardner JP, Li S, Srinivasan SR, et al. Rise in insulin resistance is associated with escalated telomere attrition. Circulation 2005; 111: 2171-7.
54. 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.
55. 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.
56. 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.
57. 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.
58. Lim PO, Struthers AD, MacDonald TM. The neurohormonal natural history of essential hypertension: towards primary or tertiary aldosteronism? J Hypertens 2002; 20: 11-5.
59. 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.
60. Benetos A, Gardner JP, Zureik M, et al. Short telomeres are associated with increased carotid atherosclerosis in hypertensive subjects. Hypertension 2004; 43: 182-5.
61. 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.
62. 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.
63. 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.
64. Takimoto E, Kass DA. Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension 2007; 49: 241-8.
65. 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.
66. Gonzalez A, Ravassa S, Lopez B, et al. Apoptosis in hypertensive heart disease: a clinical approach. Curr Opin Cardiol 2006; 21: 288-94.
67. Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003; 114: 763-76.
68. 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.
69. 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.
70. 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.
71. 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.
72. 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.
73. 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.
74. 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.
75. Buemi M, Nostro L, Aloisi C, et al. Kidney aging: from phenotype to genetics. Rejuvenation Res 2005; 8: 101-9.
76. Melk A, Ramassar V, Helms LM, et al. Telomere shortening in kidneys with age. J Am Soc Nephrol 2000; 11: 444-53.
77. 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.
78. Rosario RF, Wesson DE. Primary hypertension and nephropathy. Curr Opin Nephrol Hypertens 2006; 15: 130-4.
79. Ono H, Ono Y Nephrosclerosis and hypertension. Med Clin North Am 1997; 81: 1273-88.
80. Samani NJ, Boultby R, Butler R, et al. Telomere shortening in atherosclerosis. Lancet 2001;358: 472-3.
81. 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.
82. 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.
83. 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.
84. Fuster JJ, Diez J., Andres V. Telomere dysfunction in hypertension. Journal of Hypertension 2007, 25: 2185-92.