Platelet-derived microvesicles induce calcium oscillations and promote VSMC migration via TRPV4

Shan-Shan Li1,2, Shuang Gao1, Yi Chen1

  • 1Institute of Mechanobiology& Medical Engineering, School of Life Sciences &Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Theranostics
|January 27, 2021
PubMed

Insights

Platelet-derived microvesicles (PMVs) promote vascular smooth muscle cell (VSMC) migration by inducing calcium oscillations via the TRPV4 channel. This finding offers potential therapeutic targets for vascular injury and restenosis.

Area of Science:

  • Cardiovascular Biology
  • Cellular Biology
  • Biomedical Engineering

Background:

  • Vascular smooth muscle cell (VSMC) migration is crucial in intimal restenosis following vascular injury.
  • Platelet-derived microvesicles (PMVs) are released by activated platelets and may influence VSMC behavior.

Purpose of the Study:

  • To investigate the role of PMVs in VSMC migration.
  • To elucidate the underlying molecular mechanisms, including calcium signaling and specific ion channels.

Main Methods:

  • Vascular intimal injury model induced by balloon angioplasty in rats.
  • In vitro scratch wound healing assays to assess VSMC migration.
  • Fluorescence resonance energy transfer (FRET) to analyze intracellular calcium dynamics.
  • Pharmacological inhibition and siRNA targeting of the TRPV4 channel.

Main Results:

  • PMVs significantly enhanced VSMC migration and neointimal hyperplasia in vivo.
  • PMVs induced calcium oscillations in VSMCs, dependent on extracellular calcium influx.
  • The transient receptor potential vanilloid 4 (TRPV4) channel was identified as a key mediator of PMV-induced calcium signaling and VSMC migration.

Conclusions:

  • TRPV4 plays a critical role in mediating the effects of PMVs on VSMC migration and calcium dynamics.
  • PMVs and TRPV4 represent potential therapeutic targets for mitigating vascular remodeling after injury.

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