Overexpression of filamin c in chronic intermittent hypoxia-induced cardiomyocyte apoptosis is a potential cardioprotective target for obstructive sleep apnea

Sleep Breath. 2019 Jun;23(2):493-502. doi: 10.1007/s11325-018-1712-9. Epub 2018 Sep 7.


Purpose: Chronic intermittent hypoxia (CIH) is key pathological mechanism of obstructive sleep apnea (OSA), which induced cardiac dysfunction. Filamin c (FLNC) is a muscle-restricted isoform and predominantly expressed in muscle tissue. In this study, we utilized a recently developed CIH rat model to mimic OSA, investigated the expression of FLNC in cardiomyocytes, and examined the correlations of FLNC with active caspase-3 to ascertain whether FLNC regulates the survival of cardiomyocytes.

Methods: Forty Sprague-Dawley rats were randomly divided into normoxia and CIH groups. All rats were exposed either to normoxia or CIH 8 h daily for 6 weeks. Echocardiogram and HE staining were used to examine cardiac pathology, structure, and function. Body weight, heart weight, and blood gas values were recorded, respectively. The FLNC, Bax, Bcl-2, BNIP 3, and active caspase-3 proteins were detected by western blot; FLNC was examined by immunohistochemistry and immunofluorescence. Association of FLNC with cardiomyocyte apoptosis was detected by immunofluorescence.

Results: CIH induced cardiac injuries and caused arterial blood gas disorder. FLNC significantly increased in CIH-induced cardiomyocytes than that in normoxia tissues. Pro-apoptotic BNIP 3 and Bax proteins were significantly increased in CIH, whereas anti-apoptotic member Bcl-2 was decreased. Active caspase-3, a universal marker of apoptosis, was significantly increased in CIH group. Co-localizations of FLNC and active caspase-3 were observed in CIH group.

Conclusions: These results suggested FLNC is implicated in the pathogenesis of CIH-induced cardiomyocyte apoptosis, and FLNC may serve as a novel cardioprotective target for OSA patients.

Keywords: Cardiomyocyte apoptosis; Chronic intermittent hypoxia; FLNC; Obstructive sleep apnea.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Cardiotonic Agents*
  • Correlation of Data
  • Filamins / genetics*
  • Fluorescent Antibody Technique
  • Gene Expression Regulation / genetics*
  • Hypoxia / genetics*
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Sleep Apnea, Obstructive / genetics*
  • Sleep Apnea, Obstructive / pathology


  • Cardiotonic Agents
  • Filamins