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LncRNA ZNF593-AS alleviates diabetic cardiomyopathy via suppressing IRF3 signaling pathway

Rong Xie1,2, Jiahui Fan1,2, Jianpei Wen1,2

  • 1Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Molecular Therapy. Nucleic Acids
|May 22, 2023
PubMed

Insights

Diabetic cardiomyopathy damages the heart. The long non-coding RNA ZNF593-AS protects against this damage by suppressing inflammation and cell death, offering a new therapeutic target.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Genetics

Background:

  • Diabetes mellitus is a significant risk factor for heart disease.
  • Diabetic cardiomyopathy (DCM) presents limited therapeutic options.
  • Understanding the molecular mechanisms of DCM is crucial for developing new treatments.

Purpose of the Study:

  • To investigate the role of ZNF593-AS in diabetic cardiomyopathy.
  • To elucidate the underlying molecular mechanisms of ZNF593-AS in cardiac protection.
  • To evaluate ZNF593-AS as a potential therapeutic target for DCM.

Main Methods:

  • Generation of ZNF593-AS knockout and cardiomyocyte-specific transgenic mice.
  • Utilized high-fat diet (HFD) and db/db mouse models for DCM.
  • Employed antisense oligonucleotide (GapmeR) for gene silencing and viral vectors for overexpression.
  • Performed transcriptome sequencing, RNA pull-down, and RNA immunoprecipitation assays.

Main Results:

  • ZNF593-AS expression was reduced in diabetic hearts.
  • ZNF593-AS protected cardiomyocytes against palmitic acid-induced apoptosis.
  • ZNF593-AS deficiency exacerbated cardiac dysfunction, apoptosis, and inflammation in HFD mice.
  • ZNF593-AS overexpression ameliorated cardiac dysfunction in both HFD and db/db mice.
  • ZNF593-AS directly interacted with IRF3, suppressing its activation and downstream inflammatory signaling.

Conclusions:

  • ZNF593-AS plays a critical protective role in diabetic cardiomyopathy.
  • ZNF593-AS mitigates cardiac cell death and inflammation by inhibiting IRF3 activation.
  • ZNF593-AS represents a promising novel therapeutic target for treating diabetic cardiomyopathy.
Keywords:
IRF3MT: Non-coding RNAsZNF593-AScardiomyocytesdiabetesdiabetic cardiomyopathylncRNA

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