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Updated: Nov 19, 2025

Membrane Remodeling of Giant Vesicles in Response to Localized Calcium Ion Gradients
Published on: July 16, 2018
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.
Abstract:
Rationale: Abnormal migration of vascular smooth muscle cells (VSMCs) from the media to the interior is a critical process during the intimal restenosis caused by vascular injury. Here, we determined the role of platelet-derived microvesicles (PMVs) released by activated platelets in VSMC migration. Methods: A percutaneous transluminal angioplasty balloon dilatation catheter was used to establish vascular intimal injury. Collagen I was used to activate PMVs, mimicking collagen exposure during intimal injury. To determine the effects of PMVs on VSMC migration in vitro, scratch wound healing assays were performed. Fluorescence resonance energy transfer was used to detect variations of calcium dynamics in VSMCs. Results: Morphological results showed that neointimal hyperplasia was markedly increased after balloon injury of the carotid artery in rats, and the main component was VSMCs. PMVs significantly promoted single cell migration and wound closure in vitro. Fluorescence resonance energy transfer revealed that PMVs induced temporal and dynamic calcium oscillations in the cytoplasms of VSMCs. The influx of extracellular calcium, but not calcium from intracellular stores, was involved in the process described above. The channel antagonist GSK219 and specific siRNA revealed that a membrane calcium channel, transient receptor potential vanilloid 4 (TRPV4), participated in the calcium oscillations and VSMC migration induced by PMVs. Conclusions: TRPV4 participated in the calcium oscillations and VSMC migration induced by PMVs. PMVs and the related molecules might be novel therapeutic targets for vascular remodeling during vascular injury.
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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