二叶式主动脉瓣主动脉扩张机制的研究进展

白莹; 靳巧锋; 何书坤; 刘天舒; 邓文惠; 傅雅楠; 谭玉婷; 谢明星; 王静

doi:10.13201/j.issn.1001-1439.2023.02.004

二叶式主动脉瓣主动脉扩张机制的研究进展

- 1.
  华中科技大学同济医学院附属协和医院超声医学科(武汉，430022)
- 2.
  湖北省影像医学临床医学研究中心
- 3.
  分子影像湖北省重点实验室
基金项目:
国家自然科学基金项目(No：82171961、81771851)

详细信息

通讯作者: 王静, E-mail: jingwang2004@hust.edu.cn

中图分类号: R541.1

收稿日期: 2022-04-02

刊出日期: 2023-02-13

Research progress on the mechanism of aortic dilatation of bicuspid aortic valve

- 1.
  Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- 2.
  Clinical Research Center for Medical Imaging in Hubei Province
- 3.
  Hubei Province Key Laboratory of Molecular Imaging

More Information

Corresponding author: WANG Jing, E-mail: jingwang2004@hust.edu.cn

Received Date: 02 April 2022

Publish Date: 13 February 2023

摘要

摘要: 二叶式主动脉瓣(BAV)是最常见的先天性心脏疾病，BAV主动脉扩张与主动脉不良事件如主动脉瘤、主动脉夹层及破裂的风险增加密切相关，是一种潜在的致命性疾病。BAV主动脉疾病是遗传因素和血流动力学因素不同模式相互作用的结果，机制较为复杂。本文根据近年来BAV在基因遗传学、分子标记物、血流动力学影像标记物方面的研究进展，对其引起主动脉扩张的相关机制进行简要综述。
- 二叶式主动脉瓣 /
- 主动脉扩张 /
- 基因遗传学 /
- 血流动力学 /
- 生物标记物
Abstract: Bicuspid aortic valve(BAV) is the most common congenital heart disease. BAV aortic dilation is closely associated with an increased risk of adverse aortic events such as aortic aneurysm, aortic dissection, and rupture, and is a potentially fatal disease. The mechanism that determines aortic disease in BAV patients is complex, resulting from the interaction of different patterns between genetic factors and hemodynamic factors. Based on the research progress of BAV patients in genetics, molecular markers, and hemodynamic imaging markers in recent years, this article briefly reviews the relevant mechanisms that cause aortic dilation.
- bicuspid aortic valve /
- aortic dilation /
- genetics /
- hemodynamic /
- biomarker

HTML全文

参考文献(60)

[1]	Kong W, Bax JJ, Michelena HI, et al. Sex differences in bicuspid aortic valve disease[J]. Prog Cardiovasc Dis, 2020, 63(4): 452-456. doi: 10.1016/j.pcad.2020.06.004
[2]	Simpson JM, Pushparajah K. Dilatation of the aorta in bicuspid aortic valve disease[J]. Circ Cardiovasc Imaging, 2020, 13(3): e010448. doi: 10.1161/CIRCIMAGING.120.010448
[3]	Sievers HH, Stierle U, Hachmann RM, et al. New insights in the association between bicuspid aortic valve phenotype, aortic configuration and valve haemodynamics[J]. Eur J Cardiothorac Surg, 2016, 49(2): 439-446. doi: 10.1093/ejcts/ezv087
[4]	Michelena HI, Khanna AD, Mahoney D, et al. Incidence of aortic complications in patients with bicuspid aortic valves[J]. JAMA, 2011, 306(10): 1104-1112. doi: 10.1001/jama.2011.1286
[5]	Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease[J]. Eur Heart J, 2022, 43(7): 561-632. doi: 10.1093/eurheartj/ehab395
[6]	Antequera-González B, Martínez-Micaelo N, Alegret JM. Bicuspid aortic valve and endothelial dysfunction: current evidence and potential therapeutic targets[J]. Front Physiol, 2020, 11: 1015. doi: 10.3389/fphys.2020.01015
[7]	Sun BJ, Song JK. Bicuspid aortic valve: evolving knowledge and new questions[J]. Heart, 2022, 109(1): 10-17.
[8]	Sievers HH, Schmidtke C. A classification system for the bicuspid aortic valve from 304 surgical specimens[J]. J Thorac Cardiovasc Surg, 2007, 133(5): 1226-1233. doi: 10.1016/j.jtcvs.2007.01.039
[9]	Sádaba JR, Álvarez-Asiain V. What is in a name for bicuspid aortic valve aortopathy?[J]. Eur J Cardiothorac Surg, 2021, 60(3): 477-478. doi: 10.1093/ejcts/ezab033
[10]	Yang LT, Pellikka PA, Enriquez-Sarano M, et al. Stage B aortic regurgitation in bicuspid aortic valve: new observations on progression rate and predictors[J]. JACC Cardiovasc Imaging, 2020, 13(6): 1442-1445. doi: 10.1016/j.jcmg.2020.01.012
[11]	Murphy IG, Collins J, Powell A, et al. Comprehensive 4-stage categorization of bicuspid aortic valve leaflet morphology by cardiac MRI in 386 patients[J]. Int J Cardiovasc Imaging, 2017, 33(8): 1213-1221. doi: 10.1007/s10554-017-1107-1
[12]	Michelena HI, Corte AD, Evangelista A, et al. International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes[J]. Radiol Cardiothorac Imaging, 2021, 3(4): e200496. doi: 10.1148/ryct.2021200496
[13]	Martínez-Micaelo N, Ligero C, Antequera-González B, et al. Plasma Metabolomic profiling associates bicuspid aortic valve disease and ascending aortic dilation with a decrease in antioxidant capacity[J]. J Clin Med, 2020, 9(7).
[14]	Fletcher AJ, Syed M, Aitman TJ, et al. Inherited thoracic aortic disease: new insights and translational targets[J]. Circulation, 2020, 141(19): 1570-1587. doi: 10.1161/CIRCULATIONAHA.119.043756
[15]	Andrei AC, Yadlapati A, Malaisrie SC, et al. Comparison of outcomes and presentation in men-versus-women with bicuspid aortic valves undergoing aortic valve replacement[J]. Am J Cardiol, 2015, 116(2): 250-255. doi: 10.1016/j.amjcard.2015.04.017
[16]	Della Corte A, Bancone C, Dialetto G, et al. The ascending aorta with bicuspid aortic valve: a phenotypic classification with potential prognostic significance[J]. Eur J Cardiothorac Surg, 2014, 46(2): 240-247. doi: 10.1093/ejcts/ezt621
[17]	Dutta P, James JF, Kazik H, et al. Genetic and developmental contributors to aortic stenosis[J]. Circ Res, 2021, 128(9): 1330-1343. doi: 10.1161/CIRCRESAHA.120.317978
[18]	Mozzini C, Girelli D, Cominacini L, et al. An exploratory look at bicuspid aortic valve(bav)aortopathy: focus on molecular and cellular mechanisms[J]. Curr Probl Cardiol, 2021, 46(3): 100425. doi: 10.1016/j.cpcardiol.2019.04.005
[19]	Lee A, Wei S, Schwertani A. A notch more: molecular players in bicuspid aortic valve disease[J]. J Mol Cell Cardiol, 2019, 134: 62-68. doi: 10.1016/j.yjmcc.2019.05.018
[20]	Harrison OJ, Visan AC, Moorjani N, et al. Defective NOTCH signaling drives increased vascular smooth muscle cell apoptosis and contractile differentiation in bicuspid aortic valve aortopathy: A review of the evidence and future directions[J]. Trends Cardiovasc Med, 2019, 29(2): 61-68. doi: 10.1016/j.tcm.2018.06.008
[21]	Hirata Y, Aoki H, Shojima T, et al. Activation of the AKT pathway in the ascending aorta with bicuspid aortic valve[J]. Circ J, 2018, 82(10): 2485-2492. doi: 10.1253/circj.CJ-17-1465
[22]	Maleki S, Kjellqvist S, Paloschi V, et al. Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves[J]. Sci Rep, 2016, 6: 35712. doi: 10.1038/srep35712
[23]	Gould RA, Aziz H, Woods CE, et al. ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm[J]. Nat Genet, 2019, 51(1): 42-50. doi: 10.1038/s41588-018-0265-y
[24]	Helgadottir A, Thorleifsson G, Gretarsdottir S, et al. Genome-wide analysis yields new loci associating with aortic valve stenosis[J]. Nat Commun, 2018, 9(1): 987. doi: 10.1038/s41467-018-03252-6
[25]	Junco-Vicente A, Del RÁ, Martín M, et al. Update in biomolecular and genetic bases of bicuspid aortopathy[J]. Int J Mol Sci, 2021, 22(11).
[26]	Bravo-Jaimes K, Prakash SK. Genetics in bicuspid aortic valve disease: Where are we?[J]. Prog Cardiovasc Dis, 2020, 63(4): 398-406. doi: 10.1016/j.pcad.2020.06.005
[27]	Peterson JC, Wisse LJ, Wirokromo V, et al. Disturbed nitric oxide signalling gives rise to congenital bicuspid aortic valve and aortopathy[J]. Dis Model Mech, 2020, 13(9).
[28]	Ren P, Hughes M, Krishnamoorthy S, et al. Critical role of ADAMTS-4 in the development of sporadic aortic aneurysm and dissection in Mice[J]. Sci Rep, 2017, 7(1): 12351. doi: 10.1038/s41598-017-12248-z
[29]	Vorkapic E, Folkesson M, Magnell K, et al. ADAMTS-1 in abdominal aortic aneurysm[J]. PLoS One, 2017, 12(6): e0178729. doi: 10.1371/journal.pone.0178729
[30]	Laforest B, Andelfinger G, Nemer M. Loss of Gata5 in mice leads to bicuspid aortic valve[J]. J Clin Invest, 2011, 121(7): 2876-2887. doi: 10.1172/JCI44555
[31]	Arrington CB, Sower CT, Chuckwuk N, et al. Absence of TGFBR1 and TGFBR2 mutations in patients with bicuspid aortic valve and aortic dilation[J]. Am J Cardiol, 2008, 102(5): 629-631. doi: 10.1016/j.amjcard.2008.04.044
[32]	Folkersen L, Wågsäter D, Paloschi V, et al. Unraveling divergent gene expression profiles in bicuspid and tricuspid aortic valve patients with thoracic aortic dilatation: the ASAP study[J]. Mol Med, 2011, 17(11-12): 1365-1373. doi: 10.2119/molmed.2011.00286
[33]	Rocchiccioli S, Cecchettini A, Panesi P, et al. Hypothesis-free secretome analysis of thoracic aortic aneurysm reinforces the central role of TGF-β cascade in patients with bicuspid aortic valve[J]. J Cardiol, 2017, 69(3): 570-576. doi: 10.1016/j.jjcc.2016.05.007
[34]	Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, et al. The roles of matrix metalloproteinases and their inhibitors in human diseases[J]. Int J Mol Sci, 2020, 21(24).
[35]	Wang J, Deng W, Lv Q, et al. Aortic dilatation in patients with bicuspid aortic valve[J]. Front Physiol, 2021, 12: 615175. doi: 10.3389/fphys.2021.615175
[36]	Wang YB, Li Y, Deng YB, et al. Enlarged size and impaired elastic properties of the ascending aorta are associated with endothelial dysfunction and elevated plasma matrix metalloproteinase-2 level in patients with bicuspid aortic valve[J]. Ultrasound Med Biol, 2018, 44(5): 955-962. doi: 10.1016/j.ultrasmedbio.2018.01.012
[37]	Maguire EM, Pearce S, Xiao R, et al. Matrix metalloproteinase in abdominal aortic aneurysm and aortic dissection[J]. Pharmaceuticals(Basel), 2019, 12(3).
[38]	Girdauskas E, Petersen J, Neumann N, et al. Novel approaches for BAV aortopathy prediction-is there a need for cohort studies and biomarkers?[J]. Biomolecules, 2018, 8(3).
[39]	Wang Y, Wu B, Dong L, et al. Circulating matrix metalloproteinase patterns in association with aortic dilatation in bicuspid aortic valve patients with isolated severe aortic stenosis[J]. Heart Vessels, 2016, 31(2): 189-197. doi: 10.1007/s00380-014-0593-5
[40]	Li Y, Wang W, Li L, et al. MMPs and ADAMs/ADAMTS inhibition therapy of abdominal aortic aneurysm[J]. Life Sci, 2020, 253: 117659. doi: 10.1016/j.lfs.2020.117659
[41]	Dawson A, Li Y, Li Y, et al. Single-cell analysis of aneurysmal aortic tissue in patients with marfan syndrome reveals dysfunctional TGF-β signaling[J]. Genes(Basel), 2021, 13(1).
[42]	Forte A, Bancone C, Cobellis G, et al. A possible early biomarker for bicuspid aortopathy: circulating transforming growth factor β-1 to soluble endoglin ratio[J]. Circ Res, 2017, 120(11): 1800-1811. doi: 10.1161/CIRCRESAHA.117.310833
[43]	Bons LR, Geenen LW, van den Hoven AT, et al. Blood biomarkers in patients with bicuspid aortic valve disease[J]. J Cardiol, 2020, 76(3): 287-294. doi: 10.1016/j.jjcc.2020.02.023
[44]	Erusalimsky JD. The use of the soluble receptor for advanced glycation-end products(sRAGE)as a potential biomarker of disease risk and adverse outcomes[J]. Redox Biol, 2021, 42: 101958. doi: 10.1016/j.redox.2021.101958
[45]	Yan SF, Ramasamy R, Schmidt AM. The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature [J]. Circ Res, 2010, 106(5): 842-853. doi: 10.1161/CIRCRESAHA.109.212217
[46]	Branchetti E, Bavaria JE, Grau JB, et al. Circulating soluble receptor for advanced glycation end product identifies patients with bicuspid aortic valve and associated aortopathies[J]. Arterioscler Thromb Vasc Biol, 2014, 34(10): 2349-2357. doi: 10.1161/ATVBAHA.114.303784
[47]	Jia H, Kang L, Lu S, et al. Circulating soluble receptor of advanced glycation end product is associated with bicuspid aortic aneurysm progression via NF-κB pathway[J]. Interact Cardiovasc Thorac Surg, 2022, 34(2): 274-282. doi: 10.1093/icvts/ivab242
[48]	Natarelli L, Weber C. A non-canonical link between non-coding RNAs and cardiovascular diseases[J]. Biomedicines, 2022, 10(2).
[49]	Naito S, Petersen J, Sequeira-Gross T, et al. Bicuspid aortopathy-molecular involvement of microRNAs and MMP-TIMP[J]. Biomarkers, 2020, 25(8): 711-718. doi: 10.1080/1354750X.2020.1841297
[50]	Lu Y, Zhang L, Tao H, et al. Two microRNAs, miR-34a and miR-125a, are implicated in bicuspid aortopathy by modulating metalloproteinase 2[J]. Biochem Genet, 2022, 60(1): 286-302. doi: 10.1007/s10528-021-10085-4
[51]	Wu J, Song HF, Li SH, et al. Progressive aortic dilation is regulated by miR-17-associated miRNAs[J]. J Am Coll Cardiol, 2016, 67(25): 2965-2977. doi: 10.1016/j.jacc.2016.04.027
[52]	Naito S, Sequeira-Gross T, Petersen J, et al. Circulating microRNAs in the prediction of BAV aortopathy: do the expression patterns correlate between blood and aortic tissue?[J]. Rev Cardiovasc Med, 2022, 23(2): 47. doi: 10.31083/j.rcm2302047
[53]	Girdauskas E, Neumann N, Petersen J, et al. Expression patterns of circulating microRNAs in the risk stratification of bicuspid aortopathy[J]. J Clin Med, 2020, 9(1).
[54]	Gallo A, Agnese V, Coronnello C, et al. On the prospect of serum exosomal miRNA profiling and protein biomarkers for the diagnosis of ascending aortic dilatation in patients with bicuspid and tricuspid aortic valve[J]. Int J Cardiol, 2018, 273: 230-236. doi: 10.1016/j.ijcard.2018.10.005
[55]	Guala A, Dux-Santoy L, Teixido-Tura G, et al. Wall shear stress predicts aortic dilation in patients with bicuspid aortic valve[J]. JACC Cardiovasc Imaging, 2022, 15(1): 46-56. doi: 10.1016/j.jcmg.2021.09.023
[56]	Soulat G, Scott MB, Allen BD, et al. Association of regional wall shear stress and progressive ascending aorta dilation in bicuspid aortic valve[J]. JACC Cardiovasc Imaging, 2022, 15(1): 33-42. doi: 10.1016/j.jcmg.2021.06.020
[57]	Kheradvar A, Vannan MA, Dasi LP, et al. The effect of aortic root anatomy and vortex flow induced shear stress on the aortic valve leaflets[J]. Eur Heart J Cardiovasc Imaging, 2021, 22(9): 995-997. doi: 10.1093/ehjci/jeab031
[58]	Pasta S, Agnese V, Gallo A, et al. Shear stress and aortic strain associations with biomarkers of ascending thoracic aortic aneurysm[J]. Ann Thorac Surg, 2020, 110(5): 1595-1604. doi: 10.1016/j.athoracsur.2020.03.017
[59]	Guzzardi DG, Barker AJ, van Ooij P, et al. Valve-related hemodynamics mediate human bicuspid aortopathy: insights from wall shear stress mapping[J]. J Am Coll Cardiol, 2015, 66(8): 892-900.
[60]	Sabatino J, Wicik Z, De Rosa S, et al. MicroRNAs fingerprint of bicuspid aortic valve[J]. J Mol Cell Cardiol, 2019, 134: 98-106.