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先天性心脏病基础研究进展

艾珊珊 何爱彬

艾珊珊, 何爱彬. 先天性心脏病基础研究进展[J]. 协和医学杂志, 2021, 12(3): 291-297. doi: 10.12290/xhyxzz.2021-0055
引用本文: 艾珊珊, 何爱彬. 先天性心脏病基础研究进展[J]. 协和医学杂志, 2021, 12(3): 291-297. doi: 10.12290/xhyxzz.2021-0055
AI Shanshan, HE Aibin. Advances in Basic Research of Congenital Heart Disease[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(3): 291-297. doi: 10.12290/xhyxzz.2021-0055
Citation: AI Shanshan, HE Aibin. Advances in Basic Research of Congenital Heart Disease[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(3): 291-297. doi: 10.12290/xhyxzz.2021-0055

先天性心脏病基础研究进展

doi: 10.12290/xhyxzz.2021-0055
详细信息
    通讯作者:

    艾珊珊  电话:020-61648603,E-mail: aishanshan233@smu.edu.cn

  • 中图分类号: R541.1;R394

Advances in Basic Research of Congenital Heart Disease

More Information
  • 摘要: 先天性心脏病(congenital heart disease,CHD)是最常见的先天性缺陷类型,其病因错综复杂,包括遗传因素、非遗传因素及环境因素。参与心脏早期形态发生的转录因子、特异基因和信号通路分子的表达失调均可导致CHD。深入了解CHD的发病机制有助于采取更有效的干预策略和治疗手段,但由于CHD致病机制复杂,目前对其认识仍十分有限。因此,本文将探讨现阶段与CHD发生发展相关的遗传因素、表观遗传因素及母体营养素与代谢产物,并概述目前常用的探究CHD致病机制的研究模型,以期为临床诊疗提供理论依据。
    作者贡献:   艾珊珊负责构思并撰写论文; 何爱彬负责修订及审校论文。
    利益冲突:   无
  • 图  1  不同类型心脏畸形占先天性心脏病的比率[4]

    CoA:主动脉缩窄; ASD:房间隔缺损; TOF:法洛四联症; TGA:大动脉移位; PDA:动脉导管未闭; PS:肺动脉狭窄; AS:主动脉狭窄; AVSD:房室间隔缺损; HLHS:左心发育不全综合征; VSD:室间隔缺损

    图  2  遗传因素、表观遗传因素、环境因素相互作用及与先天性心脏病的关系[50-51]

  • [1] Wu WL, He JX, Shao XB. Incidence and mortality trend of congenital heart disease at the global, regional, and national level, 1990-2017[J]. Medicine (Baltimore), 2020, 99: e20593. doi:  10.1097/MD.0000000000020593
    [2] Warrington NM, Beaumont RN, Horikoshi M, et al. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors[J]. Nat Genet, 2019, 51: 804-814. doi:  10.1038/s41588-019-0403-1
    [3] Joshi RO, Chellappan S, Kukshal P. Exploring the Role of Maternal Nutritional Epigenetics in Congenital Heart Disease[J]. Curr Dev Nutr, 2020, 4: nzaa166. doi:  10.1093/cdn/nzaa166
    [4] Liu YJ, Chen S, Zühlke L, et al. Global birth prevalence of congenital heart defects 1970-2017: updated systematic review and meta-analysis of 260 studies[J]. Int J Epidemiol, 2019, 48: 455-463. doi:  10.1093/ije/dyz009
    [5] Campbell M. Genetic and environmental factors in cong-enital heart disease[J]. Q J Med, 1949, 18: 379-391.
    [6] Zaidi S, Brueckner M. Genetics and Genomics of Congenital Heart Disease[J]. Circ Res, 2017, 120: 923-940. doi:  10.1161/CIRCRESAHA.116.309140
    [7] McDaniell R, Warthen DM, Sanchez-Lara PA, et al. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway[J]. Am J Hum Genet, 2006, 79: 169-173. doi:  10.1086/505332
    [8] Vecoli C, Pulignani S, Foffa I, et al. Congenital heart disease: the crossroads of genetics, epigenetics and environ-ment[J]. Curr Genomics, 2014, 15: 390-399. doi:  10.2174/1389202915666140716175634
    [9] Bondy CA. Turner syndrome 2008[J]. Horm Res, 2009, 71 Suppl 1: 52-56. http://europepmc.org/abstract/MED/19153507
    [10] Meyer RE, Liu G, Gilboa SM, et al. Survival of children with trisomy 13 and trisomy 18: A multi-state population-based study[J]. Am J Med Genet A, 2016, 170A: 825-837. http://europepmc.org/abstract/MED/26663415
    [11] Tomita-Mitchell A, Mahnke DK, Struble CA, et al. Human gene copy number spectra analysis in congenital heart malformations[J]. Physiol Genomics, 2012, 44: 518-541. doi:  10.1152/physiolgenomics.00013.2012
    [12] Silversides CK, Lionel AC, Costain G, et al. Rare copy number variations in adults with tetralogy of Fallot implicate novel risk gene pathways[J]. PLoS Genet, 2012, 8: e1002843. doi:  10.1371/journal.pgen.1002843
    [13] Hitz MP, Lemieux-Perreault LP, Marshall C, et al. Rare copy number variants contribute to congenital left-sided heart disease[J]. PLoS Genet, 2012, 8: e1002903. doi:  10.1371/journal.pgen.1002903
    [14] Payne AR, Chang SW, Koenig SN, et al. Submicroscopic chromosomal copy number variations identified in children with hypoplastic left heart syndrome[J]. Pediatr Cardiol, 2012, 33: 757-763. doi:  10.1007/s00246-012-0208-9
    [15] Goldmuntz E, Paluru P, Glessner J, et al. Microdeletions and microduplications in patients with congenital heart disease and multiple congenital anomalies[J]. Congenit Heart Dis, 2011, 6: 592-602. doi:  10.1111/j.1747-0803.2011.00582.x
    [16] Jarrell DK, Lennon ML, Jacot JG. Epigenetics and Mechanobiology in Heart Development and Congenital Heart Disease[J]. Diseases, 2019, 7: 52. doi:  10.3390/diseases7030052
    [17] Feng LF, Lou JL. DNA Methylation Analysis[J]. Methods Mol Biol, 2019, 1894: 181-227.
    [18] Sheng W, Qian YY, Wang HJ, et al. DNA methylation status of NKX2-5, GATA4 and HAND1 in patients with tetralogy of fallot[J]. BMC Med Genomics, 2013, 6: 46. doi:  10.1186/1755-8794-6-46
    [19] Radhakrishna U, Albayrak S, Alpay-Savasan Z, et al. Genome-Wide DNA Methylation Analysis and Epigenetic Variations Associated with Congenital Aortic Valve Stenosis (AVS)[J]. PLoS One, 2016, 11: e0154010. doi:  10.1371/journal.pone.0154010
    [20] Zhang YJ, Sun ZX, Jia JQ, et al. Overview of Histone Modification[J]. Adv Exp Med Biol, 2021, 1283: 1-16.
    [21] Moore-Morris T, van Vliet PP, Andelfinger G, et al. Role of Epigenetics in Cardiac Development and Congenital Diseases[J]. Physiol Rev, 2018, 98: 2453-2475. doi:  10.1152/physrev.00048.2017
    [22] Blakeslee WW, Demos-Davies KM, Lemon DD, et al. Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy[J]. Pediatr Res, 2017, 82: 642-649. doi:  10.1038/pr.2017.126
    [23] Chen L, Ma YL, Kim EY, et al. Conditional ablation of Ezh2 in murine hearts reveals its essential roles in endocardial cushion formation, cardiomyocyte proliferation and survival[J]. PLoS One, 2012, 7: e31005. doi:  10.1371/journal.pone.0031005
    [24] Kobayashi J, Yoshida M, Tarui S, et al. Directed differentiation of patient-specific induced pluripotent stem cells identifies the transcriptional repression and epigenetic modification of NKX2-5, HAND1, and NOTCH1 in hypoplastic left heart syndrome[J]. PLoS One, 2014, 9: e102796. doi:  10.1371/journal.pone.0102796
    [25] Lee S, Lee JW, Lee SK. UTX, a histone H3-lysine 27 demethylase, acts as a critical switch to activate the cardiac developmental program[J]. Dev Cell, 2012, 22: 25-37. doi:  10.1016/j.devcel.2011.11.009
    [26] Lickert H, Takeuchi JK, Von Both I, et al. Baf60c is essential for function of BAF chromatin remodelling complexes in heart development[J]. Nature, 2004, 432: 107-112. doi:  10.1038/nature03071
    [27] Takeuchi JK, Lou X, Alexander JM, et al. Chromatin remodelling complex dosage modulates transcription factor function in heart development[J]. Nat Commun, 2011, 2: 187. doi:  10.1038/ncomms1187
    [28] Chen L, Fulcoli FG, Ferrentino R, et al. Transcriptional control in cardiac progenitors: Tbx1 interacts with the BAF chromatin remodeling complex and regulates Wnt5a[J]. PLoS Genet, 2012, 8: e1002571. doi:  10.1371/journal.pgen.1002571
    [29] Lange M, Kaynak B, Forster UB, et al. Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex[J]. Genes Dev, 2008, 22: 2370-2384. doi:  10.1101/gad.471408
    [30] Gu M, Zheng AB, Tu WJ, et al. Circulating LncRNAs as Novel, Non-Invasive Biomarkers for Prenatal Detection of Fetal Congenital Heart Defects[J]. Cell Physiol Biochem, 2016, 38: 1459-1471. doi:  10.1159/000443088
    [31] Cheng ZJ, Zhang QJ, Yin AW, et al. The long non-coding RNA uc. 4 influences cell differentiation through the TGF-beta signaling pathway[J]. Exp Mol Med, 2018, 50: e447. doi:  10.1038/emm.2017.278
    [32] Anderson KM, Anderson DM, McAnally JR, et al. Transcription of the non-coding RNA upperhand controls Hand2 expression and heart development[J]. Nature, 2016, 539: 433-436. doi:  10.1038/nature20128
    [33] O'Brien J, Hayder H, Zayed Y, et al. Overview of Micro-RNA Biogenesis, Mechanisms of Actions, and Circulation[J]. Front Endocrinol (Lausanne), 2018, 9: 402. doi:  10.3389/fendo.2018.00402
    [34] Tian J, An XJ, Niu L. Role of microRNAs in cardiac development and disease[J]. Exp Ther Med, 2017, 13: 3-8. doi:  10.3892/etm.2016.3932
    [35] Li D, Ji L, Liu LB, et al. Characterization of circulating microRNA expression in patients with a ventricular septal defect[J]. PLoS One, 2014, 9: e106318. doi:  10.1371/journal.pone.0106318
    [36] Sucharov CC, Sucharov J, Karimpour-Fard A, et al. Micro-RNA expression in hypoplastic left heart syndrome[J]. J Card Fail, 2015, 21: 83-88. doi:  10.1016/j.cardfail.2014.09.013
    [37] Huang JC, Li XB, Li HY, et al. Down-regulation of microRNA-184 contributes to the development of cyanotic congenital heart diseases[J]. Int J Clin Exp Pathol, 2015, 8: 14221-14227. http://europepmc.org/abstract/MED/26823736
    [38] Liu LP, Yuan YH, He XH, et al. MicroRNA-1 upregula-tion promotes myocardiocyte proliferation and suppresses apoptosis during heart development[J]. Mol Med Rep, 2017, 15: 2837-2842. doi:  10.3892/mmr.2017.6282
    [39] Liang DD, Xu XR, Deng FF, et al. miRNA-940 reduction contributes to human Tetralogy of Fallot development[J]. J Cell Mol Med, 2014, 18: 1830-1839. doi:  10.1111/jcmm.12309
    [40] Garside VC, Chang AC, Karsan A, et al. Co-ordinating Notch, BMP, and TGF-beta signaling during heart valve development[J]. Cell Mol Life Sci, 2013, 70: 2899-2917. doi:  10.1007/s00018-012-1197-9
    [41] MacGrogan D, Münch J, de la Pompa JL. Notch and interacting signalling pathways in cardiac development, disease, and regeneration[J]. Nat Rev Cardiol, 2018, 15: 685-704. doi:  10.1038/s41569-018-0100-2
    [42] Penton AL, Leonard LD, Spinner NB. Notch signaling in human development and disease[J]. Semin Cell Dev Biol, 2012, 23: 450-457. doi:  10.1016/j.semcdb.2012.01.010
    [43] Iascone M, Ciccone R, Galletti L, et al. Identification of de novo mutations and rare variants in hypoplastic left heart syndrome[J]. Clin Genet, 2012, 81: 542-554. doi:  10.1111/j.1399-0004.2011.01674.x
    [44] Lim JA, Baek HJ, Jang MS, et al. Loss of beta2-spectrin prevents cardiomyocyte differentiation and heart development[J]. Cardiovasc Res, 2014, 101: 39-47. doi:  10.1093/cvr/cvt222
    [45] Feng Y, Zhao LZ, Hong L, et al. Alteration in methylation pattern of GATA-4 promoter region in vitamin A-deficient offspring's heart[J]. J Nutr Biochem, 2013, 24: 1373-1380. doi:  10.1016/j.jnutbio.2012.11.005
    [46] Persson M, Razaz N, Edstedt Bonamy AK, et al. Maternal Overweight and Obesity and Risk of Congenital Heart Defects[J]. J Am Coll Cardiol, 2019, 73: 44-53. http://www.sciencedirect.com/science/article/pii/S0735109718390867
    [47] Pezhouman A, Engel JL, Nguyen NB, et al. Isolation and characterization of hESC-derived heart field-specific cardiomyocytes unravels new insights into their transcriptional and electrophysiological profiles[J]. Cardiovasc Res, 2021: cvab102. doi: 10.1093/cvr/cvab102.Epubaheadofprint.
    [48] Bakkers J. Zebrafish as a model to study cardiac develop-ment and human cardiac disease[J]. Cardiovasc Res, 2011, 91: 279-288. doi:  10.1093/cvr/cvr098
    [49] Nakanishi T, Markwald RR, Baldwin HS, et al. Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology[M]. Tokyo: Springer, 2016: 321-327.
    [50] Jenkins KJ, Correa A, Feinstein JA, et al. Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics[J]. Circulation, 2007, 115: 2995-3014. doi:  10.1161/CIRCULATIONAHA.106.183216
    [51] Botto LD, Mulinare J, Erickson JD. Occurrence of con-genital heart defects in relation to maternal mulitivitamin use[J]. Am J Epidemiol, 2000, 151: 878-884. doi:  10.1093/oxfordjournals.aje.a010291
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出版历程
  • 收稿日期:  2021-01-17
  • 录用日期:  2021-03-23
  • 刊出日期:  2021-05-30

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