Abstract Number: PB2097
Meeting: ISTH 2020 Congress
Background: Previously, we have reported that the BrafV637E mutation, corresponding to the human BRAFV600E mutation, plays a pivotal role in hepatocarcinogenesis induced by diethylnitrosamine (DEN) in B6C3F1 mice. The livers of transgenic mice with a hepatocyte-specific human BRAFV600E mutation weighed 4.5 times greater than that of normal mice and was entirely consisted of hepatocytes resembling the DEN-induced preneoplastic hepatocytes. However, these transgenic mice spontaneously died seven weeks after birth due to thrombotic microangiopathy in the lung and kidney.
Aims: In this study, we aim to identify the role of platelets in hepatocarcinogenesis.
Methods: The Alb-Cre/BRAFV600E transgenic and control BRAFV600E mice were given aspirin (Asp) by oral intubation from 4 to 8 weeks after birth.
Results: The liver showed thrombopoietin (TPO) overexpression, which is associated with eventual megakaryocytosis and thrombocytosis, and activated platelets were deposited in hepatic sinusoids. TPO was also overexpressed in the DEN-induced hepatic tumors, and sinusoidal platelet deposition was observed in hepatic tumors of humans and mice. In the transgenic mice, Asp administration prevented platelet activation, reduced the liver/body weight ratio, decreased the platelet deposition in the liver, kidney and lung, prevented the erythrocyte dyscrasia and ameliorated the renal/pulmonary changes. Additionally, Asp administration partially inhibited the neoplastic morphology of hepatocyte.
Conclusions: These results indicate that the macroenvironment that results from TPO overproduction by the neoplastic hepatocytes, the eventual megakaryocytosis/thrombocytosis, and the platelet activation and interaction with hepatic sinusoidal cells may contribute to hepatocarcinogenesis from a very early stage. Also, platelet inhibition may have therapeutic effect on hepatocarcinogenesis.
To cite this abstract in AMA style:Tanaka H, Horioka K, Yamazaki K, Ogawa K. Amelioration of the Pathologic Changes in the Hepatocyte-Specific BRAFV600E Mutated Mice by Administration of Aspirin [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/amelioration-of-the-pathologic-changes-in-the-hepatocyte-specific-brafv600e-mutated-mice-by-administration-of-aspirin/. Accessed February 28, 2024.
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