Cardiac hypertrophy, low blood pressure, and low aldosterone levels in mice devoid of the three circadian PAR bZip transcription factors DBP, HLF, and TEF

Am J Physiol Regul Integr Comp Physiol. 2010 Oct;299(4):R1013-9. doi: 10.1152/ajpregu.00241.2010. Epub 2010 Aug 4.


The cardiovascular system is under the control of the circadian clock, and disturbed circadian rhythms can induce cardiovascular pathologies. This cyclic regulation is probably brought about by the circadian expression of genes encoding enzymes and regulators involved in cardiovascular functions. We have previously shown that the rhythmic transcription of output genes is, in part, regulated by the clock-controlled PAR bZip transcription factors DBP (albumin D-site binding protein), HLF (hepatic leukemia factor), and TEF (thyrotroph embryonic factor). The simultaneous deletion of all three PAR bZip transcription factors leads to increased morbidity and shortened life span. In the present study, we demonstrate that Dbp/Tef/Hlf triple knockout mice develop cardiac hypertrophy and left ventricular dysfunction associated with a low blood pressure. These dysfunctions are exacerbated by an abnormal response to this low blood pressure characterized by low aldosterone levels. The phenotype of PAR bZip knockout mice highlights the importance of circadian regulators in the modulation of cardiovascular functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Aldosterone / deficiency*
  • Animals
  • Atenolol / pharmacology
  • Basic-Leucine Zipper Transcription Factors / genetics*
  • Basic-Leucine Zipper Transcription Factors / physiology
  • Blood Pressure / physiology
  • Cardiomegaly / genetics*
  • Cardiomegaly / pathology
  • Cardiovascular Physiological Phenomena
  • Circadian Rhythm / genetics*
  • Circadian Rhythm / physiology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Epithelial Sodium Channels / metabolism
  • Heart Rate / physiology
  • Hypotension / genetics*
  • Kidney / physiology
  • Male
  • Mice
  • Mice, Knockout
  • Phenotype
  • Sympathetic Nervous System / physiology
  • Transcription Factors / genetics*
  • Transcription Factors / physiology


  • Adrenergic beta-Antagonists
  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Dbp protein, mouse
  • Epithelial Sodium Channels
  • Hlf protein, mouse
  • Tef protein, mouse
  • Transcription Factors
  • Aldosterone
  • Atenolol