DNA羟甲基化调控动脉粥样硬化的研究进展

doi:10.16288/j.yczz.20-036

遗传 ›› 2020, Vol. 42 ›› Issue (7): 632-640.doi: 10.16288/j.yczz.20-036

DNA羟甲基化调控动脉粥样硬化的研究进展

胡颖楚^1,², 胡豪畅¹, 林少沂¹, 陈晓敏^1,²()

^1. 浙江大学宁波医院心血管内科,宁波 315000
^2. 浙江大学医学院,杭州 310029

收稿日期:2020-04-23 修回日期:2020-05-28 出版日期:2020-07-20 发布日期:2020-06-01
通讯作者: 陈晓敏 E-mail:cxmdoctor@126.com
作者简介:胡颖楚,在读硕士研究生,专业方向：心血管内科。E-mail: lcyxhyc@163.com
基金资助:
浙江省自然科学基金项目编号(LY19H020003);宁波市自然科学基金项目资助编号(2017A610209)

The role of DNA hydroxymethylation in the regulation of atherosclerosis

Yingchu Hu^1,², Haochang Hu¹, Shaoyi Lin¹, Xiaomin Chen^1,²()

^1. Department of Cardiology, Ningbo Hospital of Zhejiang University, Ningbo 315000, China
^2. Zhejiang University School of Medicine, Hangzhou 310029, China

Received:2020-04-23 Revised:2020-05-28 Online:2020-07-20 Published:2020-06-01
Contact: Chen Xiaomin E-mail:cxmdoctor@126.com
Supported by:
Supported by the Natural Science Foundation of Zhejiang Province No(LY19H020003);the Natural Science Foundation of Ningbo City No(2017A610209)

摘要/Abstract

摘要：

DNA羟甲基化作为一种表观遗传学修饰,对基因的表达调控起到了重要作用。近年来,越来越多的研究发现在心血管疾病中可见5-羟甲基胞嘧啶(5-hydroxymethylcytosine, 5hmC)和染色体10/11易位(ten-eleven translocation, TET)家族蛋白的异常改变,提示这些心血管疾病与DNA羟甲基化的调控密切相关。DNA羟甲基化水平与动脉粥样硬化常见的危险因素如衰老、性别、高血压和吸烟存在一定关联,并且和动脉粥样硬化发生过程中所涉及的免疫炎症反应以及内皮细胞和血管平滑肌细胞的功能相关。本文综述了DNA羟甲基化和TET家族蛋白对于动脉粥样硬化的作用机制及研究现状,以期为动脉粥样硬化的发生发展及诊断治疗提供表观遗传学方面的研究思路。

关键词: DNA羟甲基化, 动脉粥样硬化, 5hmC, TET, 表观遗传学

Abstract:

As an epigenetic modification, DNA hydroxymethylation plays a significant role in regulating gene expression. In recent years, there has been increasing evidence that suggests abnormal changes of 5-hydroxymethylcytosine (5hmC) and ten-eleven translocation (TET) family proteins in cardiovascular diseases, indicating cardiovascular diseases are closely connected with DNA hydroxymethylation. The level of DNA hydroxymethylation is affected by some common risk factors of atherosclerosis, such as aging, gender, hypertension and smoking. It is also related to the immune and inflammatory reaction involved in the process of atherosclerosis as well as the function of endothelial cells and vascular smooth muscle cells. In this review, we summarize the mechanism and research status of DNA hydroxymethylation and TET family proteins towards atherosclerosis, aiming to provide a reference for the development, diagnosis and treatment of atherosclerosis.

Key words: DNA hydroxymethylation, atherosclerosis, 5hmC, TET, epigenetics

胡颖楚, 胡豪畅, 林少沂, 陈晓敏. DNA羟甲基化调控动脉粥样硬化的研究进展[J]. 遗传, 2020, 42(7): 632-640.

Yingchu Hu, Haochang Hu, Shaoyi Lin, Xiaomin Chen. The role of DNA hydroxymethylation in the regulation of atherosclerosis[J]. Hereditas(Beijing), 2020, 42(7): 632-640.

图/表 1

参考文献 55

[1]	Zhao D, Liu J, Wang M, Zhang XG, Zhou MG.Epidemiology of cardiovascular disease in China: current features and implications.Nat Rev Cardiol, 2019, 16(4): 203-212.
[2]	Zhang JW, Xu Q, Li GL.Epigenetics in the genesis and development of cancers.Hereditas(Beijing), 2019, 41(7): 567-581.
	张競文, 续倩, 李国亮. 癌症发生发展中的表观遗传学研究. 遗传, 2019, 41(7): 567-581.
[3]	Ho SM, Tang WY.Techniques used in studies of epigenome dysregulation due to aberrant DNA methylation: an emphasis on fetal-based adult diseases.Reprod Toxicol, 2007, 23(3): 267-282.
[4]	van der Harst P, de Windt LJ, Chambers JC. Translational perspective on epigenetics in cardiovascular disease.J Am Coll Cardiol, 2017, 70(5): 590-606.
[5]	Wierda RJ, Geutskens SB, Jukema JW, Quax PH, van den Elsen PJ. Epigenetics in atherosclerosis and inflammation.J Cell Mol Med, 2010, 14(6A): 1225-1240.
[6]	Zhang YX, Gao KR, Yu SY.Progress of research on 5-hydroxymethylcytosine. Hereditas(Beijing), 2012, 34(5): 509-518.
	张燕霞, 高可润, 禹顺英. 5-羟甲基胞嘧啶的研究进展. 遗传, 2012, 34(5): 509-518.
[7]	Richa R, Sinha RP.Hydroxymethylation of DNA: an epigenetic marker.EXCLI J, 2014, 13: 592-610.
[8]	Tan L, Shi YG.Tet family proteins and 5-hydroxymethylcytosine in development and disease.Development, 2012, 139(11): 1895-902.
[9]	Wang J, Zhang KX, Lu GZ, Zhao XH.Research progress on 5hmC and TET dioxygenases in neurodevelopment and neurological diseases.Hereditas(Beijing), 2017, 39(12): 1138-1149.
	王建, 张凯翔, 芦国珍, 赵湘辉. 5-羟甲基胞嘧啶及其TET氧合酶在神经系统发育和相关疾病中的研究进展. 遗传, 2017, 39(12): 1138-1149.
[10]	Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y.Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine.Science, 2011, 333(6047): 1300-1333.
[11]	Ito S, D'Alessio AC,Taranova OV,Hong K,Sowers LC,Zhang Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification.Nature, 2010, 466(7310): 1129-1133.
[12]	Kim R, Sheaffer KL, Choi I, Won KJ, Kaestner KH.Epigenetic regulation of intestinal stem cells by Tet1- mediated DNA hydroxymethylation.Genes Dev, 2016, 30(21): 2433-2442.
[13]	Ge L, Zhang RP, Wan F, Guo DY, Wang P, Xiang LX, Shao JZ.TET2 plays an essential role in erythropoiesis by regulating lineage-specific genesvia DNA oxidative demethylation in a zebrafish model. Mol Cell Biol, 2014, 34(6):989-1002.
[14]	Gu TP, Guo F, Yang H, Wu HP, Xu GF, Liu W, Xie ZG, Shi LY, He XY, Jin SG, Iqbal K, Shi YG, Deng ZX, Szabo PE, Pfeifer GP, Li JS, Xu GL.The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes.Nature, 2011, 477(7366): 606-610.
[15]	Shimozaki K.Ten-eleven translocation 1 and 2 confer overlapping transcriptional programs for the proliferation of cultured adult neural stem cells.Cell Mol Neurobiol, 2017, 37(6): 995-1008.
[16]	Neri F, Dettori D, Incarnato D, Krepelova A, Rapelli S, Maldotti M, Parlato C, Paliogiannis P, Oliviero S.TET1 is a tumour suppressor that inhibits colon cancer growth by derepressing inhibitors of the WNT pathway.Oncogene, 2015, 34(32): 4168-4176.
[17]	Lian CG, Xu YF, Ceol C, Wu FZ, Larson A, Dresser K, Xu WJ, Tan L, Hu YQ, Zhan Q, Lee CW, Hu D, Lian BQ, Kleffel S, Yang YJ, Neiswender J, Khorasani AJ, Fang R, Lezcano C, Duncan LM, Scolyer RA, Thompson JF, Kakavand H, Houvras Y, Zon LI, Mihm MC Jr, Kaiser UB, Schatton T, Woda BA, Murphy GF, Shi YG.Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma.Cell, 2012, 150(6): 1135-1146.
[18]	Ko M, An J, Pastor WA, Koralov SB, Rajewsky K, Rao A.TET proteins and 5-methylcytosine oxidation in hematological cancers.Immunol Rev, 2015, 263(1): 6-21.
[19]	Fang SH, Li J, Xiao Y, Lee M, Guo L, Han W, Li TT, Hill MC, Hong TT, Mo W, Xu R, Zhang P, Wang F, Chang J, Zhou YB, Sun DQ, Martin JF, Huang Y.Tet inactivation disrupts YY1 binding and long-range chromatin interactions during embryonic heart development.Nat Commun, 2019, 10(1): 4297.
[20]	Wang JC, Bennett M.Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence.Circ Res, 2012, 111(2): 245-259.
[21]	Khoueiry R, Sohni A, Thienpont B, Luo X, Velde JV, Bartoccetti M, Boeckx B, Zwijsen A, Rao A, Lambrechts D, Koh KP.Lineage-specific functions of TET1 in the postimplantation mouse embryo.Nat Genet, 2017, 49(7): 1061-1072.
[22]	Johnson ND, Huang LX, Li RH, Li Y, Yang YC, Kim HR, Grant C, Wu H, Whitsel EA, Kiel DP, Baccarelli AA, Jin P, Murabito JM, Conneely KN.Age-related DNA hydroxymethylation is enriched for gene expression and immune system processes in human peripheral blood.Epigenetics, 2020, 15(3): 294-306.
[23]	Ozeki M, Salah A, Aini W, Tamaki K, Haga H, Miyagawa- Hayashino A.Abnormal localization of STK17A in bile canaliculi in liver allografts: an early sign of chronic rejection.PLoS One, 2015, 10(8): e0136381.
[24]	Yosefzon Y, David C, Tsukerman A, Pnueli L, Qiao S, Boehm U, Melamed P.An epigenetic switch repressing Tet1 in gonadotropes activates the reproductive axis.Proc Natl Acad Sci USA, 2017, 114(38): 10131-10136.
[25]	Takov K, Wu JX, Denvir MA, Smith LB, Hadoke PWF.The role of androgen receptors in atherosclerosis.Mol Cell Endocrinol, 2018, 465:82-91.
[26]	Takayama K, Misawa A, Suzuki T, Takagi K, Hayashizaki Y, Fujimura T, Homma Y, Takahashi S, Urano T, Inoue S.TET2 repression by androgen hormone regulates global hydroxymethylation status and prostate cancer progression.Nat Commun, 2015, 6: 8219.
[27]	Hurtubise J, McLellan K,Durr K,Onasanya Q,Nwabuko D,Ndisang JF. The different facets of dyslipidemia and hypertension in atherosclerosis.Curr Atheroscler Rep, 2016, 18(12): 82.
[28]	Pavlov TS, Staruschenko A.Involvement of ENaC in the development of salt-sensitive hypertension.Am J Physiol Renal Physiol, 2017, 313(2): F135-F140.
[29]	Yu ZY, Kong Q, Kone BC.Aldosterone reprograms promoter methylation to regulate αENaC transcription in the collecting cuct.Am J Physiol Renal Physiol, 2013, 305(7): F1006-F1013.
[30]	Siasos G, Tsigkou V, Kokkou E, Oikonomou E, Vavuranakis M, Vlachopoulos C, Verveniotis A, Limperi M, Genimata V, Papavassiliou AG, Stefanadis C, Tousoulis D.Smoking and atherosclerosis: mechanisms of disease and new therapeutic approaches.Curr Med Chem, 2014, 21(34): 3936-3948.
[31]	Ringh MV, Hagemann-Jensen M, Needhamsen M, Kular L, Breeze CE, Sjoholm LK, Slavec L, Kullberg S, Wahlstrom J, Grunewald J, Brynedal B, Liu Y, Almgren M, Jagodic M, Ockinger J, Ekstrom TJ.Tobacco smoking induces changes in true DNA methylation, hydroxymethylation and gene expression in bronchoalveolar lavage cells.EBioMedicine, 2019, 46: 290-304.
[32]	Zhou XL, Zhuang ZH, Wang WT, He LF, Wu H, Cao Y, Pan FY, Zhao J, Hu ZG, Sekhar C, Guo ZG.OGG1 is essential in oxidative stress induced DNA demethylation.Cell Signal, 2016, 28(9): 1163-1171.
[33]	Hansson GK, Hermansson A.The immune system in atherosclerosis.Nat Immunol, 2011, 12(3): 204-212.
[34]	Wu MY, Li CJ, Hou MF, Chu PY.New insights into the role of inflammation in the pathogenesis of atherosclerosis.Int J Mol Sci, 2017, 18(10): 2034.
[35]	Hansson GK.Inflammation, atherosclerosis, and coronary artery disease.N Engl J Med, 2005, 352(16): 1685-1695.
[36]	Han XB, Boisvert WA.Interleukin-10 protects against atherosclerosis by modulating multiple atherogenic macrophage function.Thromb Haemost, 2015, 113(3): 505-512.
[37]	Ichiyama K, Chen TT, Wang XH, Yan XW, Kim BS, Tanaka S, Ndiaye-Lobry D, Deng YH, Zou YL, Zheng P, Tian Q, Aifantis I, Wei L, Dong C.The methylcytosine dioxygenase Tet2 promotes DNA demethylation and activation of cytokine gene expression in T cells.Immunity, 2015, 42(4): 613-626.
[38]	Lal G, Bromberg JS.Epigenetic mechanisms of regulation of Foxp3 expression.Blood, 2009, 114(18): 3727-3735.
[39]	Nakatsukasa H, Oda M, Yin JH, Chikuma S, Ito M, Koga-Iizuka M, Someya K, Kitagawa Y, Ohkura N, Sakaguchi S, Koya I, Sanosaka T, Kohyama J, Tsukada YI, Yamanaka S, Takamura-Enya T, Lu QJ, Yoshimura A.Loss of TET proteins in regulatory T cells promotes abnormal proliferation, Foxp3 destabilization and IL-17 expression.Int Immunol, 2019, 31(5): 335-347.
[40]	Ravanan P, Srikumar IF, Talwar P.Autophagy: The spotlight for cellular stress responses.Life Sci, 2017, 188: 53-67.
[41]	Peng J, Yang Q, Li AF, Li RQ, Wang Z, Liu LS, Ren Z, Zheng XL, Tang XQ, Li GH, Tang ZH, Jiang ZS, Wei DH.Tet methylcytosine dioxygenase 2 inhibits atherosclerosis via upregulation of autophagy in ApoE-/- mice.Oncotarget, 2016, 7(47): 76423-76436.
[42]	Yang Q, Li XH, Li RQ, Peng J, Wang Z, Jiang ZS, Tang XQ, Peng Z, Wang Y, Wei DH.Low shear stress inhibited endothelial cell autophagy through TET2 downregulation.Ann Biomed Eng, 2016, 44(7): 2218-2227.
[43]	Xu YJ, Zheng L, Hu YW, Wang Q.Pyroptosis and its relationship to atherosclerosis.Clin Chim Acta, 2018, 476: 28-37.
[44]	Zeng ZL, Chen JJ, Wu P, Liu YM, Zhang TT, Tao J, Wu SY, Xiao JY, Wei DH, Jiang ZS, Wang Z.OxLDL induces vascular endothelial cell pyroptosis through miR-125a-5p/ TET2 pathway.J Cell Physiol, 2019, 234(5): 7475-7491.
[45]	Frismantiene A, Philippova M, Erne P, Resink TJ.Smooth muscle cell-driven vascular diseases and molecular mechanisms of VSMC plasticity.Cell Signal, 2018, 52: 48-64.
[46]	Liu RJ, Jin Y, Tang WH, Qin LF, Zhang XB, Tellides G, Hwa J, Yu J, Martin KA.Ten-eleven translocation-2 (TET2) is a master regulator of smooth muscle cell plasticity.Circulation, 2013, 128(18): 2047-2057.
[47]	Fang K, Zhang KX, Wang J, Fu ZM, Zhao XH.Advances on the profiling of 5-hydroxymethylcytosine.Hereditas (Beijing), 2016, 38(3): 206-216.
	方科, 张凯翔, 王建, 付志猛, 赵湘辉. 表观遗传学新标记—5-羟甲基胞嘧啶检测方法的研究进展. 遗传, 2016, 38(3): 206-216.
[48]	Yu M, Han DL, Hon GC, He C.Tet-assisted bisulfite sequencing (TAB-seq).Methods Mol Biol, 2018, 1708: 645-663.
[49]	Gibas P, Narmontė M, Staševskij Z, Gordevičius J, Klimašauskas S, Kriukienė E.Precise genomic mapping of 5-hydroxymethylcytosinevia covalent tether-directed sequencing. PLoS Biol, 2020, 18(4): e3000684.
[50]	Dong CR, Chen JM, Zheng JL, Liang YM, Yu T, Liu YP, Gao F, Long J, Chen HY, Zhu QH, He ZL, Hu SN, He C, Lin J, Tang YD, Zhu HB.5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic and predictive biomarkers for coronary artery disease.Clin Epigenetics, 2020, 12(1): 17.
[51]	Jiang D, Wang Y, Chang GL, Duan Q, You LN, Sun M, Hu CX, Gao L, Wu SY, Tao HM, Lu K, Zhang DY.DNA hydroxymethylation combined with carotid plaques as a novel biomarker for coronary atherosclerosis.Aging (Albany NY), 2019, 11(10): 3170-3181.
[52]	Cang S, Lu Q, Ma Y, Liu D.Clinical advances in hypomethylating agents targeting epigenetic pathways.Curr Cancer Drug Targets, 2010, 10(5): 539-545.
[53]	Zwergel C, Fioravanti R, Stazi G, Sarno F, Battistelli C, Romanelli A, Nebbioso A, Mendes E, Paulo A, Strippoli R, Tripodi M, Pechalrieu D, Arimondo PB, De Luca T, Del Bufalo D, Trisciuoglio D, Altucci L, Valente S, Mai A.Novel quinoline compounds active in cancer cells through coupled DNA methyltransferase inhibition and degradation.Cancers (Basel), 2020, 12(2): 447.
[54]	Kao YH, Cheng CC, Chen YC, Chung CC, Lee TI, Chen SA, Chen YJ.Hydralazine-induced promoter demethylation enhances sarcoplasmic reticulum Ca²+-ATPase and calcium homeostasis in cardiac myocytes.Lab Invest, 2011, 91(9): 1291-1297.
[55]	Jiang QX, Yuan H, Xing XW, Liu JJ, Huang ZJ, Du X.Methylation of adrenergic β1 receptor is a potential epigenetic mechanism controlling antihypertensive response to metoprolol.Indian J Biochem Biophys, 2011, 48(5): 301-307.

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

DNA羟甲基化调控动脉粥样硬化的研究进展

The role of DNA hydroxymethylation in the regulation of atherosclerosis

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 1

参考文献 55

相关文章 15

编辑推荐

Metrics

[1]	张向前, 李楠, 解新明. 表观遗传学综合性实验设计与探讨[J]. 遗传, 2021, 43(12): 1179-1187.
[2]	梅志超, 位竹君, 于佳慧, 冀凤丹, 解莉楠. 多组学关联分析揭示表观等位基因在拟南芥环境适应性进化中的作用及机制[J]. 遗传, 2020, 42(3): 321-331.
[3]	张競文,续倩,李国亮. 癌症发生发展中的表观遗传学研究[J]. 遗传, 2019, 41(7): 567-581.
[4]	马志鹏, 陈军. 无义突变与“遗传补偿效应”[J]. 遗传, 2019, 41(5): 359-364.
[5]	岳敏, 杨禹, 郭改丽, 秦曦明. 哺乳动物生物钟的遗传和表观遗传研究进展[J]. 遗传, 2017, 39(12): 1122-1137.
[6]	王建, 张凯翔, 芦国珍, 赵湘辉. 5-羟甲基胞嘧啶及其TET氧合酶在神经系统发育和相关疾病中的研究进展[J]. 遗传, 2017, 39(12): 1138-1149.
[7]	李元丰, 韩玉波, 曹鹏博, 孟金凤, 李海北, 秦庚, 张锋, 靳光付, 杨勇, 邬玲仟, 平杰, 周钢桥. 2015年中国医学遗传学研究领域若干重要进展[J]. 遗传, 2016, 38(5): 363-390.
[8]	张笑, 贾桂芳. RNA表观遗传修饰：N⁶-甲基腺嘌呤[J]. 遗传, 2016, 38(4): 275-288.
[9]	方科, 张凯翔, 王建, 付志猛, 赵湘辉. 表观遗传学新标记--5-羟甲基胞嘧啶检测方法的研究进展[J]. 遗传, 2016, 38(3): 206-216.
[10]	孙凌云, 李星逾, 孙志为. 原发性肝癌的表观遗传学及其治疗[J]. 遗传, 2015, 37(6): 517-527.
[11]	陈晓颖, 叶华丹, 洪青晓, 周安楠, 汤琳琳, 段世伟. DNA甲基化修饰对血管疾病稳态失衡的影响[J]. 遗传, 2015, 37(3): 221-232.
[12]	贾振伟, 高树新, 张永春, 张显华. TET蛋白的去甲基化机制及其在调控小鼠发育过程中的作用[J]. 遗传, 2015, 37(1): 34-40.
[13]	任才芳，孙红艳，王立中，张国敏，樊懿萱，颜光耀，王丹，王锋. iPSCs遗传稳定性与重编程机制的研究进展[J]. 遗传, 2014, 36(9): 879-887.
[14]	邓大君. DNA甲基化和去甲基化的研究现状及思考[J]. 遗传, 2014, 36(5): 403-410.
[15]	李美婷, 曹林林, 杨洋. 表观遗传修饰在糖脂代谢中的作用[J]. 遗传, 2014, 36(3): 200-207.