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Autophagy regulates trans fatty acid-mediated apoptosis in primary cardiac myofibroblasts

Saeid Ghavami1, Ryan H Cunnington, Behzad Yeganeh

  • 1Department of Physiology, University of Manitoba, Canada.

Biochimica Et Biophysica Acta
|October 3, 2012
PubMed

Insights

Trans fat acids (TFAs) like vaccenic acid and elaidic acid induce both apoptosis and autophagy in heart cells. Autophagy is essential for the pro-apoptotic effects of these trans fats.

Area of Science:

  • Cardiovascular Biology
  • Cellular Toxicology
  • Molecular Biology

Background:

  • Trans fats are not a single entity; individual components have distinct cellular effects.
  • Vaccenic acid (VA) and elaidic acid (EA) are prevalent trans monoenes found in ruminant fats and vegetable oils.
  • Limited knowledge exists regarding the specific mechanisms of cell death induced by individual trans fatty acids.

Purpose of the Study:

  • To investigate the mechanisms of cell death induced by vaccenic acid (VA) and elaidic acid (EA) in primary rat ventricular myofibroblasts (rVF).
  • To determine if VA and EA trigger apoptosis and/or autophagy and elucidate the relationship between these processes.

Main Methods:

  • Cell viability assessed using MTT assays.
  • Apoptosis analyzed via Flow Cytometry (FACS) and Western blotting for caspase activation and Bcl2:Bax ratio.
  • Mitochondrial membrane potential and Bax translocation evaluated.
  • Autophagy markers (LC3-β, Atg5-12, beclin-1) assessed by immunoblotting and transmission electron microscopy.
  • Gene silencing (BAX, BAK, ATG3, ATG5) used to confirm pathway involvement.

Main Results:

  • Both VA and EA significantly reduced rVF viability and induced apoptosis, evidenced by caspase activation and altered Bcl2:Bax ratio.
  • VA and EA promoted Bax translocation to mitochondria and decreased mitochondrial membrane potential.
  • VA and EA also induced macroautophagosome formation and upregulated key autophagy markers.
  • Silencing of BAX, BAK, ATG3, or ATG5 significantly inhibited VA and EA-induced cell death.

Conclusions:

  • Trans fatty acids (TFAs), specifically VA and EA, induce simultaneous apoptosis and autophagy in rat ventricular myofibroblasts.
  • Autophagy is a required pathway for the pro-apoptotic effects of TFAs in these cells.
  • These findings have potential translational value for understanding and preventing TFA-linked heart disease.

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