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Microarray analysis and functional characterization revealed NEDD4-mediated cardiomyocyte autophagy induced by

Ying Gu1, Fan Yang2, Yongchao Yu2

  • 1Department of Cardiology, Changhai Hospital, The Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China.

Cell Stress & Chaperones
|January 12, 2019
PubMed

Insights

Angiotensin II enhances cardiomyocyte autophagy, a process crucial for cellular health. This study identifies NEDD4 as a key regulator, offering potential therapeutic targets for heart disease.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cardiovascular Research

Background:

  • Autophagy is a vital cellular process for maintaining homeostasis by degrading damaged components.
  • Dysregulation of autophagy in cardiomyocytes is linked to various heart diseases.
  • The precise mechanisms governing cardiomyocyte autophagy remain largely unknown.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying angiotensin II-induced cardiomyocyte autophagy.
  • To identify key genes and pathways involved in regulating cardiomyocyte autophagy.
  • To explore the potential role of identified genes as therapeutic targets for heart diseases.

Main Methods:

  • Cardiomyocyte autophagy was induced using angiotensin II (0.1 μmol/L).
  • Autophagy markers (autophagosomes, BECN1, LC3-I/II conversion) were assessed.
  • Microarray analysis identified differentially expressed genes, followed by Gene Ontology, pathway, and network analyses (KEGG, PPI).

Main Results:

  • Angiotensin II significantly enhanced cardiomyocyte autophagy.
  • Microarray analysis revealed 197 differentially expressed genes, predominantly related to metabolism.
  • NEDD4 was identified as a crucial hub gene, with its inhibition reducing angiotensin II-induced autophagy.

Conclusions:

  • Angiotensin II treatment upregulates cardiomyocyte autophagy through specific molecular pathways.
  • NEDD4 plays a significant role in regulating cardiomyocyte autophagy.
  • Targeting NEDD4 may offer a novel therapeutic strategy for heart diseases associated with autophagic dysfunction.

Keywords:
Angiotensin IIAutophagyBioinformatics analysisCardiomyocytesNEDD4

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