成纤维细胞生长因子同源因子1在心律失常发病机制中的研究进展

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (12): 1697-1700.

成纤维细胞生长因子同源因子1在心律失常发病机制中的研究进展

秦桃, 李青, 李菊香^*

南昌大学第二附属医院心血管内科, 江西南昌 330006

收稿日期:2020-05-16 修回日期:2020-08-24 出版日期:2020-12-05 发布日期:2020-11-30
通讯作者: ^* ljx912@126.com
基金资助:
国家自然科学基金(81760065); 江西省自然科学基金重大项目(20152ACB20025)

Research progress of fibroblast growth factor homologous factor 1 in the pathogenesis of arrhythmia

QIN Tao, LI Qing, LI Ju-xiang^*

Department of Cardiovascular Medicine,the Second Affiliated Hospital of Nanchang University,Nanchang 330006,China

Received:2020-05-16 Revised:2020-08-24 Online:2020-12-05 Published:2020-11-30
Contact: ^* ljx912@126.com

摘要/Abstract

摘要： 成纤维细胞生长因子同源因子1(FHF1) 是一种细胞内信号蛋白,不与成纤维细胞生长因子受体结合的非特异性成纤维细胞生长因子。FHF1与心脏电压门控钠离子通道的C末端结合,调节Na⁺电流,进而影响心肌细胞的动作电位,促进心律失常的发生发展。

关键词: 成纤维细胞生长因子同源因子, 心律失常, 钠离子通道, 磷酸化

Abstract: Fibroblast growth factor homologous factor 1 (FHF1) is an intracellular signaling protein, a non-specific fibroblast growth factor that does not bind to fibroblast growth factor receptors. FHF1 combines with the C-terminus of cardiac voltage-gated sodium ion channels to regulate Na⁺current, which in turn affects the action potential of myocardial cells and results in arrhythmias with a higher frequence.

Key words: fibroblast growth factor homologous factor, arrhythmia, sodium channel, phosphorylation

中图分类号:

R541.7

秦桃, 李青, 李菊香. 成纤维细胞生长因子同源因子1在心律失常发病机制中的研究进展[J]. 基础医学与临床, 2020, 40(12): 1697-1700.

QIN Tao, LI Qing, LI Ju-xiang. Research progress of fibroblast growth factor homologous factor 1 in the pathogenesis of arrhythmia[J]. Basic & Clinical Medicine, 2020, 40(12): 1697-1700.

参考文献

[1] Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics-2019 update: a report from the american heart association[J]. Circulation, 2019, 139: e56-e528. doi:10.1161/CIR.0000000000000659.
[2] Jansen H, Mackasey M, Moghtadaei M, et al. Distinct patterns of atrial electrical and structural remodeling in angiotensin ii mediated atrial fibrillation[J]. J Mol Cell Cardiol,2018, 124:12-25.
[3] Munoz-Sanjuan I, Smallwood PM, Nathans J. Isoform diversity among fibroblast growth factor homologous factors is generated by alternative promoter usage and differential splicing[J]. J Biol Chem,2000, 275:2589-2597.
[4] Olsen SK, Garbi M, Zampieri N, et al. Fibroblast growth factor (fgf) homologous factors share structural but not functional homology with fgfs[J]. J Biol Chem,2003, 278:34226-34236.
[5] Schoorlemmer J, Goldfarb M. Fibroblast growth factor homologous factors and the islet brain-2 scaffold protein regulate activation of a stress-activated protein kinase[J]. J Biol Chem,2002,277:49111-49119.
[6] Liu CJ, Dib-Hajj SD, Renganathan M, et al. Modulation of the cardiac sodium channel nav1.5 by fibroblast growth factor homologous factor 1b[J]. J Biol Chem,2003, 278:1029-1036.
[7] Belau F, Metzner K, Christ T, et al. Dpp10 is a new regulator of nav1.5 channels in human heart[J]. Int J Cardiol,2019,284:68-73.
[8] Liu C, Dib-Hajj SD, Waxman SG. Fibroblast growth factor homologous factor 1b binds to the c terminus of the tetrodotoxin-resistant sodium channel rnav1.9a (nan)[J]. J Biol Chem, 2001, 276: 18925-18933.
[9] Wildburger NC, Ali SR, Hsu WC, et al. Quantitative proteomics reveals protein-protein interactions with fibroblast growth factor 12 as a component of the voltage-gated sodium channel 1.2 (nav1.2) macromolecular complex in Mammalian brain[J]. Mol Cell Proteomics, 2015, 14: 1288-1300.
[10] Takeguchi R, Haginoya K, Uchiyama Y, et al. Two Japanese cases of epileptic encephalopathy associated with an FGF12 mutation[J]. Brain Dev,2018, 40:728-732.
[11] Hegyi B, Banyasz T, Izu LT, et al. β-adrenergic regulation of late Na(+) current during cardiac action potential is mediated by both PKA and CaMKII[J]. J Mol Cell Cardiol, 2018, 123:168-179.
[12] Aizawa Y, Fujisawa T, Katsumata Y, et al. Sex-dependent phenotypic variability of an scn5a mutation: brugada syndrome and sick sinus syndrome[J]. J Am Heart Assoc,2018,7:e009387.doi: 10.1161/JAHA.118.009387.
[13] Tyan L, Foell JD, Vincent KP, et al. Long QT syndrome caveolin-3 mutations differentially modulate Kv 4 and Cav 1.2 channels to contribute to action potential prolongation[J]. J Physiol, 2019, 597: 1531-1551.
[14] Kroncke BM, Yang T, Roden DM. Multiple mechanisms underlie increased cardiac late sodium current[J]. Heart Rhythm,2019,16:1091-1097.
[15] Musa H, Kline CF, Sturm AC, et al. Scn5a variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia[J]. Proc Natl Acad Sci U S A, 2015, 112: 12528-12533.
[16] Yang HQ, Pérez-Hernández M, Sanchez-Alonso J, et al. Ankyrin-G mediates targeting of both Na⁺ and KATP Channels to the rat cardiac intercalated disc[J]. Elife,2020, 9:e52373. doi: 10.7554/eLife.52373.
[17] Hennessey JA, Marcou CA, Wang C, et al. Fgf12 is a candidate brugada syndrome locus[J]. Heart Rhythm, 2013, 10: 1886-1894.
[18] Dai S, Mehdi H, Morgan G, et al. Compound scn5a mutation and fgf12 variation cause brugada syndrome[J]. JACC, 2017, 69: 332. doi:10.1016/S0735-1097(17)33721-X.
[19] Cheniti G, Vlachos K, Meo M, et al. Mapping and ablation of idiopathic ventricular fibrillation[J]. Front Cardiovasc Med,2018, 5:123. doi: 10.3389/fcvm.2018.00123.
[20] Wang X, Tang H, Wei EQ, et al. Conditional knockout of Fgf13 in murine hearts increases arrhythmia suscepti-bility and reveals novel ion channel modulatory roles[J]. J Mol Cell Cardiol, 2017, 104:63-74.
[21] Li Q, Zhao Y, Wu G, et al. De novo fgf12 (fibroblast growth factor 12) functional variation is potentially associated with idiopathic ventricular tachycardia[J]. J Am Heart Assoc, 2017, 6. doi:10.1161/JAHA.117.006130.
[22] Burel S, Coyan FC, Lorenzini M, et al. C-terminal phosphorylation of NaV1.5 impairs fgf13-dependent regulation of channel inactivation[J]. J Biol Chem, 2017, 292: 17431-17448.