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Isolation and Culture of Adult Mouse Cardiomyocytes for Cell Signaling and in vitro Cardiac Hypertrophy
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Isolation and Culture of Adult Mouse Cardiomyocytes for Cell Signaling and in vitro Cardiac Hypertrophy

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Angiotensin-(1-9) prevents cardiomyocyte hypertrophy by controlling mitochondrial dynamics via miR-129-3p/PKIA

Cristian Sotomayor-Flores1,2, Pablo Rivera-Mejías1, César Vásquez-Trincado1

  • 1Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas & Facultad de Medicina, Universidad de Chile, Santiago, Chile.

Cell Death and Differentiation
|March 11, 2020
PubMed

Insights

Angiotensin-(1-9) peptide prevents cardiac hypertrophy by regulating mitochondrial dynamics and calcium handling. It activates protein kinase A (PKA) signaling, crucial for its anti-hypertrophic effects in cardiomyocytes.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Mitochondrial Biology

Background:

  • Cardiac hypertrophy involves mitochondrial morphology and calcium handling disturbances.
  • The noncanonical renin-angiotensin system peptide, Angiotensin-(1-9), exhibits anti-hypertrophic effects.
  • The precise mechanism of Angiotensin-(1-9) action remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which Angiotensin-(1-9) exerts its anti-hypertrophic effects.
  • To investigate the role of mitochondrial dynamics and calcium handling in Angiotensin-(1-9) action.
  • To identify signaling pathways modulated by Angiotensin-(1-9) in cardiomyocytes.

Main Methods:

  • Investigated Angiotensin-(1-9) effects on mitochondrial fusion/fission (DRP1 phosphorylation).
  • Utilized a norepinephrine-induced cardiomyocyte hypertrophy model.
  • Performed RNA-sequencing (RNA-seq) to identify microRNA changes.
  • Assessed the role of miR-129, PKIA, and PKA signaling.

Main Results:

  • Angiotensin-(1-9) promotes mitochondrial fusion via DRP1 phosphorylation.
  • Angiotensin-(1-9) prevents mitochondrial fission and calcium dysregulation in a hypertrophy model.
  • Angiotensin-(1-9) upregulates miR-129, which inhibits PKIA, activating PKA signaling.
  • PKA activity is essential for Angiotensin-(1-9)'s effects on mitochondrial dynamics, calcium handling, and anti-hypertrophic actions.

Conclusions:

  • Angiotensin-(1-9) protects against cardiac hypertrophy by modulating mitochondrial dynamics and calcium handling.
  • The PKA signaling pathway, activated by miR-129 and subsequent PKIA inhibition, mediates these protective effects.
  • This study reveals a novel mechanism for Angiotensin-(1-9) in cardiovascular protection.

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