Research status of the relationship between telomeres and cardiovascular and cerebrovascular diseases_West China Medical Journal

Authors：

TANG Yifang ¹ , TANG Qin ¹ , WANG Xiaoqing ¹ , LIN Yapeng ¹ , GUO Yijia ¹ , HAO Junli ¹ , ZHANG Xiao ² ,  YANG Jie ¹

1. Department of Neurology, the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P. R. China;
2. School of Basic Medicine, Chengdu Medical College, Chengdu, Sichuan 610500, P. R. China;

Corresponding author：

YANG Jie, Email: yangjie1126@163.com

Keywords：

Telomeres; Atherosclerosis; Cardiovascular and cerebrovascular diseases; Biomarkers

DOI：

10.7507/1002-0179.201907164

Video：

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Abstract Full text Figures/Tables Video References Cited by

Telomeres play an important role in maintaining genomic stability and cell life. Accumulating studies show that telomeres are closely related to human aging, cardiovascular diseases and cerebrovascular diseases. There are a series of researches about telomeres and atherosclerosis across the world, including studies on the relationship between atherosclerosis, cardiovascular diseases, cerebrovascular diseases and telomere length, and on telomere-targeted treatments for cardiovascular and cerebrovascular diseases. Telomeres may be a risk predictor or a new therapeutic target for atherosclerosis and cardiovascular diseases. This article reviews the relationship between telomeres and cardiovascular and cerebrovascular diseases, introduces the research progress of telomere length and cardiovascular diseases, cerebrovascular diseases, and the possible mechanisms of their association, aiming to provide a theoretical basis for exploring new therapeutic targets for atherosclerosis.

Citation： TANG Yifang, TANG Qin, WANG Xiaoqing, LIN Yapeng, GUO Yijia, HAO Junli, ZHANG Xiao, YANG Jie. Research status of the relationship between telomeres and cardiovascular and cerebrovascular diseases. West China Medical Journal, 2019, 34(10): 1170-1174. doi: 10.7507/1002-0179.201907164 Copy

1.	GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol, 2019, 18(5): 439-458.
2.	Zhou M, Wang H, Zeng X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the global burden of disease study 2017. Lancet, 2019.
3.	《中国脑卒中防治报告2018》编写组. 我国脑卒中防治仍面临巨大挑战——《中国脑卒中防治报告2018》概要. 中国循环杂志, 2019, 34(2): 105-119.
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5.	Doksani Y, Wu JY, de Lange T, et al. Super-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop formation. Cell, 2013, 155(2): 345-356.
6.	Hayashi MT. Telomere biology in aging and cancer: early history and perspectives. Genes Genet Syst, 2018, 92(3): 107-118.
7.	de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev, 2005, 19(18): 2100-2110.
8.	Li JS, Miralles Fusté J, Simavorian T, et al. TZAP: a telomere-associated protein involved in telomere length control. Science, 2017, 355(6325): 638-641.
9.	Zhang W, Hui R, Yang S. Telomeres, cardiovascular aging, and potential intervention for cellular senescence. Sci China Life Sci, 2014, 57(8): 858-862.
10.	陈宇, 刘继斌, 刘鹏, 等. 人颈动脉粥样硬化斑块组织及外周血白细胞相对端粒长度的检测及相关性分析. 中国分子心脏病学杂志, 2012, 12(1): 27-31.
11.	叶兴, 黄河浪. 端粒长度检测技术与方法进展及其优缺点比较. 广东医学, 2018, 39(1): 148-150, 155.
12.	Haycock PC, Heydon EE, Kaptoge S, et al. Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis. BMJ, 2014, 349: g4227.
13.	Tian R, Zhang LN, Zhang TT, et al. Association between oxidative stress and peripheral leukocyte telomere length in patients with premature coronary artery disease. Med Sci Monit, 2017, 23: 4382-4390.
14.	刘龙梅, 王仲朝, 李保, 等. 外周血白细胞端粒长度与早发冠心病的相关性研究. 实用检验医师杂志, 2015, 7(2): 70-72.
15.	田然, 张磊楠, 张婷婷, 等. 外周血白细胞端粒长度与早发冠心病的相关性及其影响因素分析. 中国循环杂志, 2016, 31(6): 541-545.
16.	Zhan Y, Karlsson IK, Karlsson R, et al. Exploring the causal pathway from telomere length to coronary heart disease: a network mendelian randomization study. Circ Res, 2017, 121(3): 214-219.
17.	Hunt SC, Kimura M, Hopkins PN, et al. Leukocyte telomere length and coronary artery calcium. Am J Cardiol, 2015, 116(2): 214-218.
18.	Carty CL, Kooperberg C, Liu J, et al. Leukocyte telomere length and risks of incident coronary heart disease and mortality in a racially diverse population of postmenopausal women. Arterioscler Thromb Vasc Biol, 2015, 35(10): 2225-2231.
19.	Huang S, Ding R, Lin Y, et al. Reduced T-cell thymic export reflected by sj-TREC in patients with coronary artery disease. J Atheroscler Thromb, 2016, 23(5): 632-643.
20.	Satoh M, Nasu T, Takahashi Y, et al. Expression of miR-23a induces telomere shortening and is associated with poor clinical outcomes in patients with coronary artery disease. Clin Sci (Lond), 2017, 131(15): 2007-2017.
21.	Satoh M, Minami Y, Takahashi Y, et al. Effect of intensive lipid-lowering therapy on telomere erosion in endothelial progenitor cells obtained from patients with coronary artery disease. Clin Sci (Lond), 2009, 116(11): 827-835.
22.	Satoh M, Takahashi Y, Tabuchi T, et al. Cellular and molecular mechanisms of statins: an update on pleiotropic effects. Clin Sci (Lond), 2015, 129(2): 93-105.
23.	Zhang W, Chen Y, Wang Y, et al. Short telomere length in blood leucocytes contributes to the presence of atherothrombotic stroke and haemorrhagic stroke and risk of post-stroke death. Clin Sci (Lond), 2013, 125(1): 27-36.
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25.	Li J, Feng C, Li L, et al. The association of telomere attrition with first-onset stroke in Southern Chinese: a case-control study and meta-analysis. Sci Rep, 2018, 8(1): 2290.
26.	Xiao J, Yuan Q, Zhang S, et al. The telomere length of peripheral blood cells is associated with the risk of ischemic stroke in han population of northern China. Medicine (Baltimore), 2019, 98(7): e14593.
27.	Zee RY, Castonguay AJ, Barton NS, et al. Relative leukocyte telomere length and risk of incident ischemic stroke in men: a prospective, nested case-control approach. Rejuvenation Res, 2010, 13(4): 411-414.
28.	李静, 张梅, 余传庆, 等. 外周血白细胞相对端粒长度与脑卒中的相关研究. 中国分子心脏病学杂志, 2015, 15(6): 1529-1533.
29.	陈宇, 王玉瑶, 范靖尧, 等. 外周血白细胞端粒长度与初发卒中患者心脑血管死亡风险的关系. 中国卒中杂志, 2013, 8(5): 368-374.
30.	李丹青. 外周血白细胞端粒长度与大动脉粥样硬化性脑梗死及颈动脉粥样硬化斑块稳定性的相关研究. 合肥: 安徽医科大学, 2017.
31.	李静. 动脉粥样硬化性脑梗死患者外周血白细胞相对端粒长度的相关性研究. 蚌埠: 蚌埠医学院, 2017.
32.	吴奇, 韩东阳, 李昕. 外周血白细胞DNA相对端粒长度与进展性脑梗死患病风险的关联性. 东南国防医药, 2019, 21(2): 135-140.
33.	Martin-Ruiz C, Dickinson HO, Keys B, et al. Telomere length predicts poststroke mortality, dementia, and cognitive decline. Ann Neurol, 2006, 60(2): 174-180.
34.	周亚飞. 急性脑梗死患者认知功能障碍相关影响因素研究. 济南: 济南大学, 2015.
35.	D’Mello MJ, Ross SA, Briel M, et al. Association between shortened leukocyte telomere length and cardiometabolic outcomes: systematic review and meta-analysis. Circ Cardiovasc Genet, 2015, 8(1): 82-90.
36.	Jin X, Pan B, Dang X, et al. Relationship between short telomere length and stroke: a meta-analysis. Medicine (Baltimore), 2018, 97(39): e12489.
37.	Gao D, Zhang R, Ji G, et al. Relative telomere length and stroke risk in a Chinese han population. J Mol Neurosci, 2018, 66(4): 475-481.
38.	Maeda T, Oyama JI, Higuchi Y, et al. The correlation between the telomeric parameters and the clinical laboratory data in the patients with brain infarct and metabolic disorders. J Nutr Health Aging, 2010, 14(9): 793-797.
39.	Zhang D, Wen X, Wu W, et al. Homocysteine-related hTERT DNA demethylation contributes to shortened leukocyte telomere length in atherosclerosis. Atherosclerosis, 2013, 231(1): 173-179.
40.	肖健豪, 袁倩, 张斯淼, 等. 外周血PON1基因高甲基化、端粒长度变短与脑梗死发病相关. 临床与病理杂志, 2019, 39(5): 1002-1009.
41.	Borghini A, Cervelli T, Galli A, et al. DNA modifications in atherosclerosis: from the past to the future. Atherosclerosis, 2013, 230(2): 202-209.
42.	Yin H, Pickering JG. Cellular senescence and vascular disease: novel routes to better understanding and therapy. Can J Cardiol, 2016, 32(5): 612-623.
43.	Erusalimsky JD, Kurz DJ. Cellular senescence in vivo: its relevance in ageing and cardiovascular disease. Exp Gerontol, 2005, 40(8/9): 634-642.
44.	Erusalimsky JD. Vascular endothelial senescence: from mechanisms to pathophysiology. J Appl Physiol (1985), 2009, 106(1): 326-332.
45.	李燕, 段君, 王玉瑶. 端粒、端粒酶在动脉粥样硬化中的研究进展. 生命的化学, 2018, 38(3): 473-477.
46.	雷江, 田卫峰, 刘毅龙. 端粒与心血管疾病的关系. 现代医学与健康研究电子杂志, 2018, 2(15): 180-183.
47.	黄四春, 姜昕, 郭毅. 端粒长度与心脑血管疾病. 实用医学杂志, 2011, 27(16): 3066-3068.
48.	吕涛, 郭文怡. 端粒长度与心血管疾病危险因素关系的研究进展. 心脏杂志, 2018, 30(5): 575-579, 593.
49.	肖滨, 黄小波. 衰老与动脉粥样硬化关系的研究进展. 中华老年多器官疾病杂志, 2018, 17(11): 866-869.
50.	Scheller Madrid A, Rode L, Nordestgaard BG, et al. Short telomere length and ischemic heart disease: observational and genetic studies in 290022 individuals. Clin Chem, 2016, 62(8): 1140-1149.
51.	Telomeres Mendelian Randomization Collaboration. Association between telomere length and risk of cancer and non-neoplastic diseases: a mendelian randomization study. JAMA Oncol, 2017, 3(5): 636-651.
52.	Codd V, Nelson CP, Albrecht E, et al. Identification of seven loci affecting mean telomere length and their association with disease. Nat Genet, 2013, 45(4): 422-427.
53.	Liang Y, Zhang R, Zhang S, et al. Association of ACYP2 and TSPYL6 genetic polymorphisms with risk of ischemic stroke in han Chinese population. Mol Neurobiol, 2017, 54(8): 5988-5995.
54.	Wu Y, Wang X, Zhou X, et al. Temporal expression of apelin/apelin receptor in ischemic stroke and its therapeutic potential. Front Mol Neurosci, 2017, 10: 1.
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1. GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol, 2019, 18(5): 439-458.
2. Zhou M, Wang H, Zeng X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the global burden of disease study 2017. Lancet, 2019.
3. 《中国脑卒中防治报告2018》编写组. 我国脑卒中防治仍面临巨大挑战——《中国脑卒中防治报告2018》概要. 中国循环杂志, 2019, 34(2): 105-119.
4. 李梅, 赵雪芹, 王同兆, 等. 动脉粥样硬化的发病机制及治疗的综述. 科技视界, 2017(26): 35-36, 52.
5. Doksani Y, Wu JY, de Lange T, et al. Super-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop formation. Cell, 2013, 155(2): 345-356.
6. Hayashi MT. Telomere biology in aging and cancer: early history and perspectives. Genes Genet Syst, 2018, 92(3): 107-118.
7. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev, 2005, 19(18): 2100-2110.
8. Li JS, Miralles Fusté J, Simavorian T, et al. TZAP: a telomere-associated protein involved in telomere length control. Science, 2017, 355(6325): 638-641.
9. Zhang W, Hui R, Yang S. Telomeres, cardiovascular aging, and potential intervention for cellular senescence. Sci China Life Sci, 2014, 57(8): 858-862.
10. 陈宇, 刘继斌, 刘鹏, 等. 人颈动脉粥样硬化斑块组织及外周血白细胞相对端粒长度的检测及相关性分析. 中国分子心脏病学杂志, 2012, 12(1): 27-31.
11. 叶兴, 黄河浪. 端粒长度检测技术与方法进展及其优缺点比较. 广东医学, 2018, 39(1): 148-150, 155.
12. Haycock PC, Heydon EE, Kaptoge S, et al. Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis. BMJ, 2014, 349: g4227.
13. Tian R, Zhang LN, Zhang TT, et al. Association between oxidative stress and peripheral leukocyte telomere length in patients with premature coronary artery disease. Med Sci Monit, 2017, 23: 4382-4390.
14. 刘龙梅, 王仲朝, 李保, 等. 外周血白细胞端粒长度与早发冠心病的相关性研究. 实用检验医师杂志, 2015, 7(2): 70-72.
15. 田然, 张磊楠, 张婷婷, 等. 外周血白细胞端粒长度与早发冠心病的相关性及其影响因素分析. 中国循环杂志, 2016, 31(6): 541-545.
16. Zhan Y, Karlsson IK, Karlsson R, et al. Exploring the causal pathway from telomere length to coronary heart disease: a network mendelian randomization study. Circ Res, 2017, 121(3): 214-219.
17. Hunt SC, Kimura M, Hopkins PN, et al. Leukocyte telomere length and coronary artery calcium. Am J Cardiol, 2015, 116(2): 214-218.
18. Carty CL, Kooperberg C, Liu J, et al. Leukocyte telomere length and risks of incident coronary heart disease and mortality in a racially diverse population of postmenopausal women. Arterioscler Thromb Vasc Biol, 2015, 35(10): 2225-2231.
19. Huang S, Ding R, Lin Y, et al. Reduced T-cell thymic export reflected by sj-TREC in patients with coronary artery disease. J Atheroscler Thromb, 2016, 23(5): 632-643.
20. Satoh M, Nasu T, Takahashi Y, et al. Expression of miR-23a induces telomere shortening and is associated with poor clinical outcomes in patients with coronary artery disease. Clin Sci (Lond), 2017, 131(15): 2007-2017.
21. Satoh M, Minami Y, Takahashi Y, et al. Effect of intensive lipid-lowering therapy on telomere erosion in endothelial progenitor cells obtained from patients with coronary artery disease. Clin Sci (Lond), 2009, 116(11): 827-835.
22. Satoh M, Takahashi Y, Tabuchi T, et al. Cellular and molecular mechanisms of statins: an update on pleiotropic effects. Clin Sci (Lond), 2015, 129(2): 93-105.
23. Zhang W, Chen Y, Wang Y, et al. Short telomere length in blood leucocytes contributes to the presence of atherothrombotic stroke and haemorrhagic stroke and risk of post-stroke death. Clin Sci (Lond), 2013, 125(1): 27-36.
24. Ding H, Chen C, Shaffer JR, et al. Telomere length and risk of stroke in Chinese. Stroke, 2012, 43(3): 658-663.
25. Li J, Feng C, Li L, et al. The association of telomere attrition with first-onset stroke in Southern Chinese: a case-control study and meta-analysis. Sci Rep, 2018, 8(1): 2290.
26. Xiao J, Yuan Q, Zhang S, et al. The telomere length of peripheral blood cells is associated with the risk of ischemic stroke in han population of northern China. Medicine (Baltimore), 2019, 98(7): e14593.
27. Zee RY, Castonguay AJ, Barton NS, et al. Relative leukocyte telomere length and risk of incident ischemic stroke in men: a prospective, nested case-control approach. Rejuvenation Res, 2010, 13(4): 411-414.
28. 李静, 张梅, 余传庆, 等. 外周血白细胞相对端粒长度与脑卒中的相关研究. 中国分子心脏病学杂志, 2015, 15(6): 1529-1533.
29. 陈宇, 王玉瑶, 范靖尧, 等. 外周血白细胞端粒长度与初发卒中患者心脑血管死亡风险的关系. 中国卒中杂志, 2013, 8(5): 368-374.
30. 李丹青. 外周血白细胞端粒长度与大动脉粥样硬化性脑梗死及颈动脉粥样硬化斑块稳定性的相关研究. 合肥: 安徽医科大学, 2017.
31. 李静. 动脉粥样硬化性脑梗死患者外周血白细胞相对端粒长度的相关性研究. 蚌埠: 蚌埠医学院, 2017.
32. 吴奇, 韩东阳, 李昕. 外周血白细胞DNA相对端粒长度与进展性脑梗死患病风险的关联性. 东南国防医药, 2019, 21(2): 135-140.
33. Martin-Ruiz C, Dickinson HO, Keys B, et al. Telomere length predicts poststroke mortality, dementia, and cognitive decline. Ann Neurol, 2006, 60(2): 174-180.
34. 周亚飞. 急性脑梗死患者认知功能障碍相关影响因素研究. 济南: 济南大学, 2015.
35. D’Mello MJ, Ross SA, Briel M, et al. Association between shortened leukocyte telomere length and cardiometabolic outcomes: systematic review and meta-analysis. Circ Cardiovasc Genet, 2015, 8(1): 82-90.
36. Jin X, Pan B, Dang X, et al. Relationship between short telomere length and stroke: a meta-analysis. Medicine (Baltimore), 2018, 97(39): e12489.
37. Gao D, Zhang R, Ji G, et al. Relative telomere length and stroke risk in a Chinese han population. J Mol Neurosci, 2018, 66(4): 475-481.
38. Maeda T, Oyama JI, Higuchi Y, et al. The correlation between the telomeric parameters and the clinical laboratory data in the patients with brain infarct and metabolic disorders. J Nutr Health Aging, 2010, 14(9): 793-797.
39. Zhang D, Wen X, Wu W, et al. Homocysteine-related hTERT DNA demethylation contributes to shortened leukocyte telomere length in atherosclerosis. Atherosclerosis, 2013, 231(1): 173-179.
40. 肖健豪, 袁倩, 张斯淼, 等. 外周血PON1基因高甲基化、端粒长度变短与脑梗死发病相关. 临床与病理杂志, 2019, 39(5): 1002-1009.
41. Borghini A, Cervelli T, Galli A, et al. DNA modifications in atherosclerosis: from the past to the future. Atherosclerosis, 2013, 230(2): 202-209.
42. Yin H, Pickering JG. Cellular senescence and vascular disease: novel routes to better understanding and therapy. Can J Cardiol, 2016, 32(5): 612-623.
43. Erusalimsky JD, Kurz DJ. Cellular senescence in vivo: its relevance in ageing and cardiovascular disease. Exp Gerontol, 2005, 40(8/9): 634-642.
44. Erusalimsky JD. Vascular endothelial senescence: from mechanisms to pathophysiology. J Appl Physiol (1985), 2009, 106(1): 326-332.
45. 李燕, 段君, 王玉瑶. 端粒、端粒酶在动脉粥样硬化中的研究进展. 生命的化学, 2018, 38(3): 473-477.
46. 雷江, 田卫峰, 刘毅龙. 端粒与心血管疾病的关系. 现代医学与健康研究电子杂志, 2018, 2(15): 180-183.
47. 黄四春, 姜昕, 郭毅. 端粒长度与心脑血管疾病. 实用医学杂志, 2011, 27(16): 3066-3068.
48. 吕涛, 郭文怡. 端粒长度与心血管疾病危险因素关系的研究进展. 心脏杂志, 2018, 30(5): 575-579, 593.
49. 肖滨, 黄小波. 衰老与动脉粥样硬化关系的研究进展. 中华老年多器官疾病杂志, 2018, 17(11): 866-869.
50. Scheller Madrid A, Rode L, Nordestgaard BG, et al. Short telomere length and ischemic heart disease: observational and genetic studies in 290022 individuals. Clin Chem, 2016, 62(8): 1140-1149.
51. Telomeres Mendelian Randomization Collaboration. Association between telomere length and risk of cancer and non-neoplastic diseases: a mendelian randomization study. JAMA Oncol, 2017, 3(5): 636-651.
52. Codd V, Nelson CP, Albrecht E, et al. Identification of seven loci affecting mean telomere length and their association with disease. Nat Genet, 2013, 45(4): 422-427.
53. Liang Y, Zhang R, Zhang S, et al. Association of ACYP2 and TSPYL6 genetic polymorphisms with risk of ischemic stroke in han Chinese population. Mol Neurobiol, 2017, 54(8): 5988-5995.
54. Wu Y, Wang X, Zhou X, et al. Temporal expression of apelin/apelin receptor in ischemic stroke and its therapeutic potential. Front Mol Neurosci, 2017, 10: 1.
55. Kong Q, Hao Y, Li X, et al. HDAC4 in ischemic stroke: mechanisms and therapeutic potential. Clin Epigenetics, 2018, 10(1): 117.
56. 米雪楠. MicroRNAs对血管内皮细胞衰老及血管功能影响的研究. 北京: 北京协和医学院, 2015.
57. Benetos A, Kark JD, Toupance S, et al. Response by benetos et al to letter regarding article, "short leukocyte telomere length precedes clinical expression of atherosclerosis: the blood-and-muscle model". Circ Res, 2018, 122(8): e73-e74.
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