Abstract Number: PB0768
Meeting: ISTH 2022 Congress
Background: Besides their hemostatic functions, platelets play an important role in liver diseases by interacting with circulatory and liver-resident (immune) cells such as hepatocytes, Kupffer cells, and stellate cells. The most common chronic liver disease is non-alcoholic fatty liver disease (NAFLD), which is characterized by excessive accumulation of hepatic triglycerides and eventually progresses into non-alcoholic steatohepatitis (NASH) and liver fibrosis/cirrhosis. Platelets accumulate in steatotic livers of NAFLD patients and potentially contribute to hepatic inflammation and endoplasmic reticulum (ER) stress.
Aims: The central aim of this project is to elucidate the role of platelets in the development of hepatic ER stress, lipid accumulation, and inflammation.
Methods: Mice were treated with tunicamycin to induce hepatic ER stress and depleted of platelets using an anti-GPIb-antibody. Hepatic tissue was analyzed on mRNA, protein, and lipid levels. Furthermore, immune cell influx was determined by flow cytometry and histological stainings. Additionally, in vitro studies were performed by coincubation of platelets with murine hepatocytes.
Results: Tunicamycin led to a significant increase of hepatic triglycerides, which was associated with elevated hepatic expression of very-low-density lipoprotein receptor (VLDLR). Depletion of platelets alleviated hepatic steatosis and lowered plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST). In addition, the absence of platelets significantly decreased markers of ER stress and mRNA levels of interleukin-1b. In contrast to the in vivo data, in vitro co-incubation of platelets with hepatocytes did not alter ER stress and only mildly affected lipid accumulation, indicating the need for an additional (immune) cell type.
Conclusion(s): Platelets exert detrimental effects on ER stress-induced hepatic steatosis by interacting with (liver-resident) immune cells.
To cite this abstract in AMA style:Derler M, Schrottmaier W, Salzmann M, Schoiswohl G, Schmid J, Assinger A, Mussbacher M. The role of platelets in ER stress-induced hepatic steatosis [abstract]. https://abstracts.isth.org/abstract/the-role-of-platelets-in-er-stress-induced-hepatic-steatosis/. Accessed September 27, 2022.
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