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Live Cell Imaging during Mechanical Stretch
07:42

Live Cell Imaging during Mechanical Stretch

Published on: August 19, 2015

Involvement of death receptor signaling in mechanical stretch-induced cardiomyocyte apoptosis

Xudong Liao1, Xiaohui Wang, Ying Gu

  • 1Cardiovascular Institute and Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100037, P.R. China.

Life Sciences
|May 3, 2005
PubMed

Insights

Mechanical stress triggers cardiomyocyte apoptosis via death receptor signaling, activating caspases and releasing cytochrome c. This pathway, involving Fas and TRAIL, contributes to heart cell death.

Area of Science:

  • Cardiovascular Biology
  • Cellular Signaling
  • Apoptosis Research

Background:

  • Mechanical overload and abnormal blood pressure induce cardiovascular apoptosis.
  • Intracellular signaling pathways for cardiomyocyte apoptosis are not fully understood.
  • Previous studies linked stretch-induced apoptosis to RAS and mitochondrial pathways.

Purpose of the Study:

  • To investigate the role of death receptor signaling in mechanical stretch-induced cardiomyocyte apoptosis.
  • To elucidate the specific molecular mechanisms involved in this process.

Main Methods:

  • Utilized an in vitro model of mechanical stretch on neonatal rat cardiomyocytes.
  • Analyzed the activation of caspases (8, 9, 3), death receptors (Fas, FasL), and death ligands (TRAIL).
  • Assessed the impact of exogenous TRAIL, soluble death receptor (sDR5), and dominant-negative FADD (FADD-DN) on apoptosis and mitochondrial integrity.

Main Results:

  • Mechanical stretch activated death receptor signaling, including caspases 8, 9, and 3.
  • Up-regulation of Fas and FasL expression and cell surface trafficking of FasL and TRAIL were observed.
  • Exogenous TRAIL exacerbated stretch-induced apoptosis, while sDR5 neutralized it.
  • FADD-DN significantly inhibited apoptosis, caspase activation, and mitochondrial cytochrome c release.

Conclusions:

  • Mechanical stretch activates FADD-linked death receptor signaling in cardiomyocytes.
  • This pathway contributes to cardiomyocyte apoptosis, potentially by activating mitochondria-dependent signaling.

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