Effect of Bmal1 regulation of T⁃type calcium channel on the circadian rhythm of chronic heart failure ventricular arrhythmias
CSTR:
Author:
Affiliation:

Clc Number:

Fund Project:

  • Article
  • |
  • Figures
  • |
  • Metrics
  • |
  • Reference
  • |
  • Related
  • |
  • Cited by
  • |
  • Materials
  • |
  • Comments
    Abstract:

    Objective:This study aims to Explore the effect of circadian clock gene of brain and muscle ARNT-like protein-1(Bmal1)regulated T-type calcium channel(TTCC)on circadian rhythm of chronic heart failure(CHF)ventricular arrhythmia(VA)and its possible mechanisms. Methods:The C57BL/6J mice CHF model was established by transverse aortic constriction(TAC) and mice in control group(CON) were treated with sham operation. Some TAC mice were randomly assigned to receive TTCC inhibitor mibefradil(MIB) for 2 weeks(CHF+MIB). Cardiac function was assessed by echocardiographic and the expression level of TTCC was determined by immune histochemical(IHC)staining and Western blot(WB). Ventricular arrhythmia(VA)was induced through programmed electrical stimulation(PES) in each group. The circadian rhythms of Bmal1 and TTCC were detected by WB and real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR),and the molecular mechanism by which Bmal1 regulated TTCC was determined by chromatin immunoprecipitation(ChIP). Results:Compared with CON group,CHF mice had significantly reduced cardiac systolic function,increased internal diameter accompanied by obvious cardiac hypertrophy. Significantly increased TTCC re-expression level in CHF mice myocardium was detected by IHC staining and WB. PES indicated that VA occurrence was significantly increased when comparing CHF mice with CON mice. To a certain extent,using MIB could reduce the occurrence of VA in CHF mice. In addition,VA occurrence appeared circadian rhythm in all three groups(CON,CHF and CHF+MIB). WB and qRT-PCR results suggested that the expressions of Bmal1 and TTCC in the myocardium of CHF mice exhibited circadian rhythm and ChIP suggested that Bmal1 could directly bind to the E-box site of TTCC promoter to regulate TTCC. Conclusion:In CHF mice,TTCC channel is highly re-expressed and shows circadian rhythm,and MIB can reduce the occurrence of VA in CHF mice. Bmal1 can directly bind to the E-box site of TTCC promoter region to regulate the transcription of TTCC.

    Reference
    Related
    Cited by
Get Citation

俞 灏,周子皓,张南南,薛思源,钱智勇,王 垚,邹建刚. Bmal1调控T型钙离子通道对慢性心衰室性心律失常昼夜节律的影响[J].南京医科大学学报(自然科学版英文版),2022,42(5):611-618.

Copy
Share
Article Metrics
  • Abstract:
  • PDF:
  • HTML:
  • Cited by:
History
  • Received:
  • Revised:
  • Adopted:
  • Online: May 23,2022
  • Published:
Article QR Code