Journal of Shandong University (Health Sciences) ›› 2020, Vol. 58 ›› Issue (5): 27-37.doi: 10.6040/j.issn.1671-7554.0.2020.192

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LncRNA056298 mediates the occurrence of neural remodeling recurrence in radiofrequency ablation dogs by affecting the expression of growth associated protein 43

LIU Donglu, WANG Ximin, LI Zhan, DU Juanjuan, LI Jianhua, MA Shenzhou, HOU Yinglong   

  1. Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong, China
  • Published:2022-09-27

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Abstract: Objective To investigate the mechanism of intrinsic autonomic remodeling after radiofrequency ablation in order to provide theoretical basis for mechanism of atrial fibrillation recurrence. Methods A total of 12 healthy adult mongrel dogs were randomly divided into 1-month radiofrequency ablation group, 1-month negative control group, 6-month radiofrequency ablation group and 6-month negative control group, with 3 dogs in each group. In the control groups, only thoracotomy was performed; in the ablation groups, the right upper and right lower ganglia were ablated, and atrial tissues 1 cm around the ablation were harvested after 1 month and 6 months of feeding for high-throughput second-generation sequencing to identify the differentially expressed long non-coding RNAs(lncRNAs)and predict their target genes. Another 12 healthy adult mongrel dogs were selected and randomly divided into the negative control group(intramuscular injection of LncRNA056298 negative control lentivirus into the right atrium)and overexpressing group(intramuscular injection of LncRNA056298 overexpressing lentivirus into the right atrium), with 6 dogs in either group. The atrial effective refractory period(AERP)and induction rate of atrial fibrillation were detected before lentivirus injection and 10 days after the injection. The right atria of the experimental dogs were collected to detect the mRNA and protein expressions of LncRNA056298 and GAP43 with qRT-PCR and Western blotting. The changes of metrics related to intrinsic autonomic remodeling were detected with immunohistochemistry, such as choline acetyltransferase(CHAT), tyrosine hydroxylase(TH), growth associated protein 43(GAP43)and protein gene product 9.5(PGP9.5). Results Differentially expressed lncRNA056298 and target gene GAP43 were screened out via bioinformatics analysis. Ten days after injection of lentivirus overexpressing lncRNA056298 into experimental animals, AERP was significantly shorter than before(95.000 vs 85.000, Z=-3.012, P=0.008). However, there was no significant difference in AERP before and after injection with negative control lentivirus(92.500 vs 95.000, Z=0.842, P=0.600). The results of atrial fibrillation induction exhibited that atrial fibrillation was induced in 3 dogs in the overexpressing group, whereas there was no atrial fibrillation induced in the negative control group. Immunohistochemistry indicated that compared with negative control group, the overexpressing group had significantly increased expressions of GAP43, TH, CHAT and PGP9.5. Conclusion LncRNA056298 can affect the occurrence of intrinsic autonomic remodeling by affecting the expression of GAP43. Intrinsic autonomic remodeling may be an important factor affecting the recurrence of atrial fibrillation after radiofrequency ablation.

Key words: Atrial fibrillation, Neural remodeling, Radiofrequency ablation, Long non-coding RNA, LncRNA056298, Growth associated protein 43

CLC Number: 

  • R541.7
[1] 李建华, 贾晓萌, 侯应龙. 心房颤动的现代治疗概况[J]. 中国心脏起搏与心电生理杂志,2017,31(6):572-575.
[2] Upadhyay GA, Alenghat FJ. Catheter ablation for atrial fibrillation in 2019[J]. JAMA, 2019, 322(7): 686-687.
[3] 金慧, 张振刚, 袁晓晨. 非瓣膜性心房颤动卒中风险评估研究进展[J]. 国际心血管病杂志,2019,46(6):324-327.
[4] Schotten U, Verheule S, Kirchhof P, et al. Pathophysiological mechanisms of atrial fibrillation: a translational appraisal[J]. Physiol Rev, 2011, 91(1): 265-325.
[5] Sakamotos S, Schuessler RB, Lee AM, et al. Vagal denervation and reinnervation after ablation of ganglionated plexi [J]. J Thorac Cardiovasc Surg, 2010, 139(2): 444-452.
[6] Jin Q, Zhao Z, Zhao Q, et al. Long noncoding RNAs: emerging roles in pulmonary hypertension[J]. Herat Fail Rev, 2019, 18. doi: 10.1007/s10741-019-09866-2.
[7] Wu ZY, Trenner M, Boon RA, et al. Long noncoding RNAs in key cellular processes involved in aortic aneurysms[J]. Atherosclerosis, 2020, 292: 112-118. doi: 10.1016/j. atherosclerosis.2019.11.013.
[8] Zhang BF, Jiang H, Chen J, et al. LncRNA H19 ameliorates myocardial infarction-induced myocardial injury and maladaptive cardiac remodelling by regulating KDM3A[J]. J Cell Mol Med, 2020, 24(1): 1099-1115.
[9] Chen X, Ge W, Hu J, et al. Inhibition of prostaglandin E2 receptor 4 by lnc000908 to promote the endothelial-mesenchymal transition participation in cardiac remodeling[J]. J Cell Mol Med, 2019, 23(9): 6355-6367.
[10] Ponnusamy M, Liu F, Zhang YH, ea al. Long noncoding RNA CPR(Cardiomyocyte Proliferation Regulator)regulates cardiomyocyte proliferation and cardiac repair[J]. Circulation, 2019, 139(23): 2668-2684.
[11] Lv X, Li J, Hu Y, et al. Overexpression of miR-27b-3p targeting wnt3a regulates the signaling pathway of wnt/β-catenin and attenuates atrial fibrosis in rats with atrial fibrillation[J]. Oxid Med Cell Longev, 2019, 2019: 5703764. doi:10.1155/2019/5703764.
[12] Leucci E, Patella F, Waage J, et al. MicroRNA-9 targets the long non-coding RNA MALAT1 for degradation in the nucleus[J]. Sci Rep, 2013, 3: 2535. doi: 10.1038/srep02535.
[13] Terricabras M, Piccini JP, Verma A. Ablation of persistent atrial fibrillation: challenges and solutions[J]. J Cardiovasc Electrophysiol, 2019. doi: 10.1111/jce.14311.
[14] Maurer T, Blomström-Lundqvist C, Tilz R, et al. What have we learned of ablation procedures for atrial fibrillation?[J]. J Intern Med, 2016, 279(5): 439-448.
[15] Sugumar H, Nanayakkara S, Chieng D, et al. Arrhythmia recurrence is more common in females undergoing multiple catheter ablation procedures for persistent atrial fibrillation: Time to close the gender gap[J]. Heart Rhythm, 2019. doi: 10.1016/j. hrthm.2019.12.013.
[16] Xintarakou A, Tzeis S, Psarras S, et al. Atrial fibrosis as a dominant factor for the development of atrial fibrillation: facts and gaps [J]. Europace, 2020, 22(3): 342-351.
[17] Li Z, Wang X, Wang W, et al. Altered long non-coding RNA expression profile in rabbit atria with atrial fibrillation: TCONS_00075467 modulates atrial electrical remodeling by sponging miR-328 to regulate CACNA1C[J]. J Mol Cell Cardiol, 2017, 108: 73-85. doi: 10.1016/j.yjmcc.2017.05.009.
[18] Sauer WH, McKernan ML, Li D, et al. Clinical predictors and outcomes associated with acute return of pulmonary vein conduction during pulmonary vein isolation for treatment of atrial fibrillation. [J]. Heart Rhythm, 2006, 3(9): 1024-1028.
[19] Wang LY, Shen H, Yang Q, et al. LncRNA-LINC00472 contributes to the pathogenesis of atrial fibrillation(Af)by reducing expression of JP2 and RyR2 via miR-24[J]. Biomed Pharmacother, 2019, 120: 109364. doi: 10.1016/j.biopha.2019.109364.
[20] Lu J, Xu FQ, Guo JJ, et al. Long noncoding RNA GAS5 attenuates cardiac fibroblast proliferation in atrial fibrillation via repressing ALK5[J]. Eur Rev Med Pharmacol Sci, 2019, 23(17): 7605-7610.
[21] Gao F, Li Z, Ding WM, et al. LncRNA PVT1 regulates atrial fibrosis via miR-128-3p-SP1-TGF-β1-Smad axis in atrial fibrillation[J]. Mol Med, 2019, 25(1): 7.
[22] Shen C, Kong B, Liu Y, et al. YY1-induced upregulation of LncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by modulating miR-384b/CACNA1C axis[J]. Biochem Biophys Res Commun, 2018, 505(1): 134-140.
[23] Yang M, Zhang S, Liang J, et al. Different effects of norepinephrine and nerve growth factor on atrial fibrillation vulnerability[J]. J Cardiol, 2019, 74(5): 460-465.
[24] Barbaro MR, Cremon C, Fuschi D, et al. Nerve fiber overgrowth in patients with symptomatic diverticular disease[J]. Neurogastroenterol Motil, 2019, 31(9): 13575.
[25] Mohan A, Thalamuthu A, Mather KA, et al. Differential expression of synaptic and interneuron genes in the aging human prefrontal cortex[J]. Neurobiol Aging, 2018, 70: 194-202. doi: 10.1016/j.neurobiolaging.2018.06.011.
[26] Gao W, He X, Li Y, et al. The effects of FK1706 on nerve regeneration and bladder function recovery following an end-to-side neurorrhaphy in rats[J]. Oncotarget, 2017, 8(55): 94345-94357.
[27] Honer WG, Falkai P, Chen C, et al. Synaptic and plasticity-associated proteins in anterior frontal cortex in severe mental illness[J]. Neuroscience, 1999, 91(4): 1247-1255.
[28] Xiong XX, Pan F, Chen RQ, et al. Neuroglobin boosts axon regeneration during ischemic reperfusion via p38 binding and activation depending on oxygen signal[J]. 2018, 9(2): 163.
[29] Singh B, Krishnan A, Micu I, et al. Peripheral neuron plasticity is enhanced by brief electrical stimulation and overrides attenuated regrowth in experimental diabetes[J]. Neurobiol Dis, 2015, 83: 134-151.doi: 10.1016/j.nbd.2015.08.009.
[30] Wang X, Zhang M, Zhang Y, et al. Long-term effects of ganglionated plexi ablation on electrophysiological characteristics and neuron remodeling in target atrial tissues in a canine model [J]. Circ Arrhythm Electrophysiol, 2015, 8(5): 1276-1283.
[31] Hung CC, Lin CH, Chang H, et al. Astrocytic GAP43 Induced by the TLR4/NF-κB/STAT3 axis attenuates astrogliosis-mediated microglial activation and neurotoxicity[J]. J Neurosic, 2016, 36(6): 2027-2043.
[32] Sanna MD, Quattrone A, Ghelardini C, et al. PKC-mediated HuD-GAP43 pathway activation in a mouse model of antiretroviral painful neuropathy [J]. Pharmacol Res, 2014, 81: 44-53. doi: 10.1016/j.phrs.2014.02.004.
[33] Li BO, Wang ZJ, Yu M, et al. miR-22-3p enhances the intrinsic regenerative abilities of primary sensory neurons via the CBL/p-EGFR/p-STAT3/GAP43/p-GAP43 axis [J]. J Cell Physiol, 2020, 235(5): 4605-4617.
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