Journal of Shandong University (Health Sciences) ›› 2019, Vol. 57 ›› Issue (4): 1-8.doi: 10.6040/j.issn.1671-7554.0.2018.706

    Next Articles

Roles and mechanisms of TCONS_00016478 in atrial energy metabolic remodeling by regulating PGC-1α/ PPARγ pathway in rabbit models of atrial fibrillation

LI Jianhua, LI Zhan, JIA Xiaomeng, DU Juanjuan, MA Shenzhou, LIU Donglu, ZHANG Yong, ZHANG Yujiao, HOU Yinglong   

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

PDF (PC)

131

Abstract: Objective To investigate the roles and mechanisms of TCONS_00016478 in atrial energy metabolic remodeling by regulating peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)/ peroxisome proliferator-activated receptor gamma(PPARγ)pathway in rabbit models of atrial fibrillation(AF). Methods The long non-coding RNA(lncRNA)expression profiles of right atria were investigated in AF and non-AF rabbit models using RNA sequencing technique. A total of 18 male and female adult New Zealand white rabbits weighting 2.0~2.5 kg were randomly divided into 3 groups: sham group(n=6, received thoracotomy only), negative control group(n=6, right atria infected with negative control lentiviruses), and lenti-RNAi-TCONS_00016478 group(n=6, right atria infected with TCONS_00016478 silencing lentiviruses). The atrial effective refractory period(AERP)and AF inducibility were measured before infection and 7 d after infection. After 7 d infection, the rabbits were sacrificed and atrial samples were collected. The gene and protein expressions were detected with qRT-PCR and Western blotting, respectively. The accumulation of glycogens and lipid droplets in atrial myocytes were assessed with periodic acid-Schiff(PAS)and Oil Red O staining, respectively. Results After 7 d infection, the AERP was significantly shortened in lenti-RNAi-TCONS_00016478 group(80.667±1.453 vs 71.750±2.411, t=3.168, P=0.034); however, no significant difference was found in the sham group(80.083±1.044 vs 79.333±0.333, t=0.684, P=0.531)and negative control group(81.083±2.599 vs 80.000±2.646, t=0.022, P=0.983). AF was induced in 3 rabbits in lenti-RNAi-TCONS_00016478 group, while no AF was induced in the sham and negative control groups. There were significant differences in the gene and protein expressions of TCONS_00016478(F=126.042, P<0.001), PGC1-α(F=43.998, P<0.001), PPARγ(F=417.863, P<0.001), glucose transporter type 4(GLUT4)(F=98.043, P<0.001) and carnitine palmitoyltransferase 1(CPT1)(F=105.096, P<0.001) among the 3 groups. Compared with the sham group, the lenti-RNAi-TCONS_00016478 group had lower expressions of TCONS_00016478, PGC1-α, PPARγ, GLUT4, and CPT1(all P<0.001), Bioinformatic analysis showed lncRNA TCONS_00016478 and PGC-1α were closely related to myocardial energy metabolism. But significantly increased accumulation of glycogens and lipid droplets in atrial myocytes. Conclusion TCONS_00016478 modulates atrial energy metabolic remodeling during AF through PGC-1α/PPARγ pathway.

Key words: Atrial fibrillation, Atrial energy metabolic remodeling, Long non-coding RNA, TCONS_00016478, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha, Peroxisome proliferator-activated receptor gamma

CLC Number: 

  • R541.7
[1] Lip GY, Tse HF, Lane DA. Atrial fibrillation[J]. Lancet, 2012, 379(9816): 648-661.
[2] Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS[J]. Europace, 2016, 18(11): 1609-1678.
[3] Schoonderwoerd BA, Van Gelder IC, Van Veldhuisen DJ, et al. Electrical and structural remodeling: role in the genesis and maintenance of atrial fibrillation[J]. Prog Cardiovasc Dis, 2005, 48(3): 153-168.
[4] Nattel S, Harada M. Atrial remodeling and atrial fibrillation: recent advances and translational perspectives[J]. J Am Coll Cardiol, 2014, 63(22): 2335-2345.
[5] van Bilsen M, Smeets PJ, Gilde AJ, et al. Metabolic remodelling of the failing heart: the cardiac burn-out syndrome?[J]. Cardiovasc Res, 2004, 61(2): 218-226.
[6] Kretz M, Webster DE, Flockhart RJ, et al. Suppression of progenitor differentiation requires the long noncoding RNA ANCR[J]. Genes & development, 2012, 26(4): 338-343.
[7] Cesana M, Cacchiarelli D, Legnini I, et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA[J]. Cell, 2011, 147(2): 358-369.
[8] Heo JB, Sung S. Vernalization-mediated epigenetic silencing by a long intronic noncoding RNA[J]. Science, 2011, 331(6013): 76-79.
[9] Sallam T, Sandhu J, Tontonoz P. Long noncoding RNA discovery in cardiovascular disease: decoding form to function[J]. Circulation Research, 2018, 122(1): 155-166.
[10] Han P, Li W, Lin CH, et al. A long noncoding RNA protects the heart from pathological hypertrophy[J]. Nature, 2014, 514(7520): 102-106.
[11] Kumarswamy R, Bauters C, Volkmann I, et al. Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure[J]. Circ Res, 2014, 114(10): 1569-1575.
[12] Wang K, Long B, Zhou LY, et al. CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation[J]. Nat Commun, 2014, 5: 3596. doi: 10.1038/ncomms4596.
[13] 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.
[14] Wang W, Wang X, Zhang Y, et al. Transcriptome analysis of canine cardiac fat pads: involvement of two novel long non-coding RNAs in atrial fibrillation neural remodeling[J]. J Cell Biochem, 2015, 116: 809-821. doi: 10.1002/jcb.25037.
[15] Ruan Z, Sun X, Sheng H, et al. Long non-coding RNA expression profile in atrial fibrillation[J]. Int J Clin Exp Pathol, 2015, 8(7): 8402-8410.
[16] Puigserver P. Tissue-specific regulation of metabolic pathways through the transcriptional coactivator PGC1-alpha[J]. Int J Obes, 2005, 29: 5-9. doi: 10.1038/sj.ijo.0802905.
[17] Cannavino J, Brocca L, Sandri M, et al. PGC1-α over-expression prevents metabolicalterations and soleus muscle atrophy in hindlimb unloaded mice[J]. J Physiol, 2014, 592(20): 4575-4589.
[18] Spiegelman BM. Transcriptional control of mitochondrial energy metabolism through the PGC1 coactivators[J]. Novartis Found Symp, 2007, 287: 60-69. doi: 10.1002/9780470985571.ch2.
[19] Lopaschuk GD, Ussher JR, Folmes CD, et al. Myocardial fatty acid metabolism in health and disease[J]. Physiol Rev, 2010, 90(1): 207-258.
[20] Soccio RE, Li Z, Chen ER, et al. Targeting PPARγ in the epigenome rescues genetic metabolic defects in mice[J]. J Clin Invest, 2017, 127(4): 1451-1462.
[21] Kurhe Y, Mahesh R. Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice[J]. Neurobiol Stress, 2016, 3: 114-121. doi: org/10.1016/j.ynstr.
[22] Karsdal MA, Henriksen K, Genovese F, et al. Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes[J]. Diabetologia, 2017, 60(1): 50-59.
[23] Liu GZ, Hou TT, Yuan Y, et al. Fenofibrate inhibits atrial metabolic remodelling in atrial fibrillation through PPAR-α/sirtuin 1/PGC-1α pathway[J]. Br J Pharmacol, 2016, 173(6): 1095-1109.
[24] Townsend KL, An D, Lynes MD, et al. Increased mitochondrial activity in BMP7-treated brown adipocytes, due to increased CPT1- and CD36-mediated fatty acid uptake[J]. Antioxid Redox Signal, 2013, 19(3): 243-257.
[25] Chen YP, Tsai CW, Shen CY, et al. Palmitic acid interferes with energy metabolism balance by adversely switching the SIRT1-CD36-fatty acid pathway to the PKC zeta-GLUT4-glucose pathway in cardiomyoblasts[J]. J Nutr Biochem, 2016, 31: 137-149. doi: 10.1016/j.jnutbio.2016.01.007.
[26] Guttman M, Rinn JL. Modular regulatory principles of large non-coding RNAs[J]. Nature, 2012, 482(7385): 339-346.
[1] LU Xiang-Dong, YANG Wei, XU Guang-Meng, QU Yuan-Ming. Expression and role of PPAR-γin meningiomas and troglitazone induced meningiomas cell apoptosis in vitro [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 65-.
[2] ZHANG Yan, YANG Xinyan, LIN Mingjie, ZHANG Kai, RONG Bing, CHEN Tongshuai, XU Xingsheng, SUN Hui, HAN Wenqiang, LAN Qingsu, LIU Xinlei, WANG Juntao, ZHONG Jingquan. Energy selection strategy for atrial fibrillation ablation: cryo, heat, laser, and electroporation [J]. Journal of Shandong University (Health Sciences), 2025, 63(11): 105-116.
[3] DONG Yaqi, WANG Xinhui, ZHAO Yinghui, WANG Chuanxin. Clinical value of serum exosomal LINC02163 as a marker for distant metastasis of colorectal cancer [J]. Journal of Shandong University (Health Sciences), 2023, 61(9): 19-28.
[4] ZHONG Lili, SHENG Ying, GUO Jianghong, YANG Shuangjian, HE Yijing. LncRNA-UCA1 effects invasion and metastasis of trophoblast cells by targeting miR-182-5p [J]. Journal of Shandong University (Health Sciences), 2022, 60(3): 76-82.
[5] ZHAO Yaqing, XU Jingwen, WANG Xiao, HOU Yinglong, GAO Mei. Mechanism of hydrogen sulfide in improving atrial fibrillation induced by obstructive sleep apnea based on oxidative stress [J]. Journal of Shandong University (Health Sciences), 2022, 60(12): 7-12.
[6] FENG Xinxin, HAN Bo, ZHANG Li, MA Mengjie, CHEN Siyu. Long non-coding RNA NONHSAT247814.1 expression in 18 childhood with myocarditis and in vitro cellular experimental observation [J]. Journal of Shandong University (Health Sciences), 2022, 60(10): 27-32.
[7] HUANG Huining, DU Juanjuan, SUN Yi, HOU Yinglong, GAO Mei. Hydrogen sulfide alleviates acute obstructive sleep apnea-induced atrial fibrillation by regulating oxidative stress through glutaredoxin-1 [J]. Journal of Shandong University (Health Sciences), 2022, 60(1): 1-5.
[8] LI Wanwan, ZHOU Wenkai, DONG Shuqing, HE Shiqing, LIU Zhao, ZHANG Jiaxin, LIU Bin. Construct of a risk assessment model of breast cancer immune-related lncRNAs based on the database information [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 74-84.
[9] CAI Fanfan, JI Congshan, YANG Shifeng, GU Hui, YUAN Xianshun, LIU Hongwu, QIN Songnan, GAO Lin, WANG Ruopeng, WANG Ximing. Clinical application of third-generation double-source CT in coronary CT angiography for patients with atrial fibrillation [J]. Journal of Shandong University (Health Sciences), 2021, 59(2): 14-18.
[10] HUANG Bosong, CONG Hongliang. Anticoagulant therapy of non-valvular atrial fibrillation in 1,430 middle-aged patients with moderate-risk thromboembolism [J]. Journal of Shandong University (Health Sciences), 2021, 59(10): 49-67.
[11] DU Tiantian, LI Juan, ZHAO Yinghui, DUAN Weili, WANG Jing, WANG Yunshan, DU Lutao, WANG Chuanxin. Expression profiles of long non-coding RNA LINC02474 and effects on cell proliferation in colorectal cancer [J]. Journal of Shandong University (Health Sciences), 2021, 59(10): 59-69.
[12] LIU Donglu, WANG Ximin, LI Zhan, DU Juanjuan, LI Jianhua, MA Shenzhou, HOU Yinglong. LncRNA056298 mediates the occurrence of neural remodeling recurrence in radiofrequency ablation dogs by affecting the expression of growth associated protein 43 [J]. Journal of Shandong University (Health Sciences), 2020, 58(5): 27-37.
[13] YANG Xuemei, LI Juan, WANG Yifan, LI Peilong, WANG Yunshan, DU Lutao, WANG Chuanxin. Significance of a three-lncRNAs signature on the prediction of survival for HER2 positive breast cancer patients [J]. Journal of Shandong University (Health Sciences), 2020, 58(5): 69-76.
[14] LIU Xiaojing, XIA Xiyan, XIAO Ke, CHEN Wendan, ZHUANG Xuewei. Expression and clinical significance of exosomal long non-coding RNA OGFRP1 in 84 cases of non-small cell lung cancer [J]. Journal of Shandong University (Health Sciences), 2020, 58(11): 71-75.
[15] CHEN Linlin, YI Shaolei, WANG Weizong, LI Zhan, ZHANG Yong, ZHANG Yujiao,REN Manyi, XIE Xinxing, LIU Tongbao, HOU Yinglong. Risk factors of recurrent atrial fibrillation after radiofrequency catheter ablation [J]. Journal of Shandong University (Health Sciences), 2019, 57(3): 49-57.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd