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

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.

SUBMITTER: Li SS

PROVIDER: S-EPMC7797689 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Li Shan-Shan SS Gao Shuang S Chen Yi Y Bao Han H Li Zi-Tong ZT Yao Qing-Ping QP Liu Ji-Ting JT Wang Yingxiao Y Qi Ying-Xin YX

Theranostics 20210101 5

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 expo ...[more]

PMID: 33500733

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Project description:BackgroundTraumatic brain injury (TBI) can result in an acute coagulopathy including platelet dysfunction that can contribute to ongoing intracranial hemorrhage. Previous studies have shown adenosine diphosphate (ADP)-induced platelet aggregation to be reduced after TBI. In addition, circulating microvesicles (MVs) are increased following TBI and have been shown to play a role in post-TBI coagulopathy and platelet function. We hypothesized that post-TBI MVs would affect platelet aggregation in a murine head injury model.MethodsModerate TBI was performed using a weight-drop method in male C57BL6 mice. Whole blood, plasma, MVs, and MV-poor plasma were isolated from blood collected 10 minutes following TBI and were mixed separately with whole blood from uninjured mice. Platelet aggregation was measured with Multiplate impedance platelet aggregometry in response to ADP. The ADP P2Y12 receptor inhibitor, R-138727, was incubated with plasma and MVs from TBI mice, and platelet inhibition was again measured.ResultsWhole blood taken from 10-minute post-TBI mice demonstrated diminished ADP-induced platelet aggregation compared with sham mice. When mixed with normal donor blood, post-TBI plasma and MVs induced diminished ADP-induced platelet aggregation compared with sham plasma and sham MVs. By contrast, the addition of post-TBI MV-poor plasma to normal blood did not change ADP-induced platelet aggregation. The observed dysfunction in post-TBI ADP platelet aggregation was prevented by the pretreatment of post-TBI plasma with R-138727. Treatment of post-TBI MVs with R-138727 resulted in similar findings of improved ADP-induced platelet aggregation compared with nontreated post-TBI MVs.ConclusionAdenosine diphosphate-induced platelet aggregation is inhibited acutely following TBI in a murine model. This platelet inhibition is reproduced in normal blood by the introduction of post-TBI plasma and MVs. Furthermore, observed platelet dysfunction is prevented when post-TBI plasma and MVs are treated with an inhibitor of the P2Y12 ADP receptor. Clinically observed post-TBI platelet dysfunction may therefore be partially explained by the presence of the ADP P2Y12 receptor within post-TBI MVs.Level of evidenceLevel III.

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

Publications

Platelet-derived microvesicles induce calcium oscillations and promote VSMC migration <i>via</i> TRPV4.

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