Abstract Number: PB1036
Meeting: ISTH 2021 Congress
Background: A complex interaction between cells and molecules contributes to four phases of wound healing, i.e., hemostasis, inflammation, proliferation, and maturation. Platelet-expressed glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2) function in maintaining vascular integrity to prevent intra-tissue bleeding during skin inflammation. A recent study has shown that lacking both GPVI and CLEC-2 on platelets facilitates wound healing in mice through the impairment of vascular integrity and the associated fibrin/fibrinogen deposition and decreased inflammation. Dasatinib has previously been demonstrated to inhibit Src and Syk, the downstream molecules upon GPVI and CLEC-2 activation, in platelets.
Aims: In this study, we investigated whether dasatinib affects skin wound healing.
Methods: A single full-thickness excisional skin wound (4-mm diameter) was generated on dorsum of 8-week-old C57BL/6 mice. Dasatinib (5 mg/kg or 10 mg/kg) or DMSO (3%) vehicle was intraperitoneally injected immediately after biopsy and then daily for up to 3 days post injury (the inflammatory phase). Wound closure was monitored until day 9 post-injury.
Results: The results showed that dasatinib-treated mice had a significant acceleration in wound closure compared to DMSO-treated mice (n=8). However, there was no difference in wound closure between the two dasatinib-treated groups. During the first 3 days after injury, redness at the wound edge was observed in dasatinib-injected animals but not in controls. In addition, macroscopic observation of inner side of the wound revealed bleeding into the wound of dasatinib-injected mice, suggesting a loss of vascular integrity during this period. Moreover, mice treated with dasatinib had increased fibrinogen content in the wound relative to controls (n=5-6) at day 3 post injury.
Conclusions: In conclusion, our results show that dasatinib induces vascular leakage during inflammatory phase of cutaneous wound repair, leading to increased fibrinogen deposition in association with the accelerated rate of wound closure.
To cite this abstract in AMA style:Wichaiyo S, Svasti S, Morales N. Dasatinib Impairs Vascular Integrity and Promotes Skin Wound Healing in Mice [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/dasatinib-impairs-vascular-integrity-and-promotes-skin-wound-healing-in-mice/. Accessed September 23, 2021.
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