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

   

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

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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
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