PB0760 - Wilson's disease - platelet function and platelet-related novel biomarkers for hepatic manifestation

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

MW

Marta Wolska

MD, PhD Candidate
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
Warsaw, Mazowieckie, Poland
ZW

Zofia Wicik

Postdoctoral Researcher / Bioinformatician
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
Warsaw, Mazowieckie, Poland
SA

Sara Ahmadova

Research Assistant
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
Warsaw, Mazowieckie, Poland
AN

Anna Nowak

MD, PhD Candidate
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
Warsaw, Mazowieckie, Poland
AG

Aleksandra Gasecka

Associate Professor
Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
Warsaw, Mazowieckie, Poland
MP

Marek Postula

Professor
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
Warsaw, Mazowieckie, Poland
AC

Anna Czlonkowska

Professor
2nd Department of Neurology Institute of Psychiatry and Neurology Warsaw Poland
Warsaw, Mazowieckie, Poland

Presenting Author(s)

CE

Ceren Eyileten Postula

Associate Professor
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
Warsaw, Mazowieckie, Poland

Background: Wilson’s Disease (WD) is an autosomal–recessive disorder of copper metabolism caused by ATP7B mutations. However, the fundamental question of why only some patients primarily manifest with liver and/or neurological disease remains.

Aims: We anticipate that platelets and their regulators, such as non-coding RNAs impact the hepatic and neurological manifestation of WD. Therefore we aimed to analyze the platelets function and platelet-related ncRNAs expression changes in WD.

Methods: Platelet function test (impedance aggregometry), in silico prediction, and qRT-PCR validation analysis were performed. 103 patients with Wilson’s disease and 52 age, gender-matched control individuals were included.

Results: a) In silico prediction: Pathway enrichment analysis showed that Platelet activation, signaling and aggregation and Platelet degradation were identified on the 3rd and 4th place in terms of significance in WD based on genes network analysis. We identified 5 miRNAs, top targets from gene WD and Fibrosis and ATP7B gene, 4 lncRNAs and 9 circRNAs were identified. The in silico results also suggest that ncRNAs play a critical role in pathophysiology of liver fibrosis due to increased platelet activation (fig1). b) platelet activation: Impedance aggregometry showed that patients with hepatic form had significantly higher platelet activation than control in both TRAP and AA-induced test (p=0.02; p=0.03, respectively). c) qPCR: MALAT, HOTAIR and H19 lncRNAs expressions were found significantly higher in hepatic-involved patients than the control (p=0.003, p=0.04, p=0.001, respectively) (fig2).

Conclusion(s): Pathway enrichment analysis supported our hypothesis and wet-lab analysis validated the role of platelet activity in WD pathology. For the first time, we found increased platelet activation, and platelet-related lncRNAs in WD patients with hepatic form compared to healthy individuals. Our results may provide for the first time knowledge on the molecular background of platelets reactivity along with ncRNAs interactions in contribution to clinical manifestation of WD focusing on its role in liver fibrosis processes.