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Isolation of Tissue Extracellular Vesicles from the Liver
Published on: August 21, 2019
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SILAC-Based Characterization of Plasma-Derived Extracellular Vesicles in Patients Undergoing Partial Hepatectomy
Ulrike Resch1,2, Hubert Hackl3, David Pereyra4
1Department of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria.
International Journal of Molecular Sciences
|October 16, 2024
Summary
Extracellular vesicles (EVs) in plasma show distinct protein signatures linked to post-hepatectomy liver failure (PHLF). These EV proteomic signatures, reflecting cell damage, are detectable before liver surgery, offering potential prognostic markers for PHLF.
Area of Science:
- Hepatology
- Proteomics
- Nanomedicine
Background:
- Post-hepatectomy liver failure (PHLF) is a critical complication after liver surgery.
- Current prognostic markers and regenerative treatments for PHLF are insufficient.
- Plasma-derived nanoparticles, such as extracellular vesicles (EVs), may offer insights into liver regeneration and stress.
Purpose of the Study:
- To investigate the proteomic profiles of plasma extracellular vesicles (EVs) in patients undergoing partial hepatectomy (PHx).
- To identify EV protein signatures associated with the development of post-hepatectomy liver failure (PHLF).
- To determine if these EV proteomic signatures are present prior to PHx.
Main Methods:
- Plasma EVs were isolated from nine patients (three PHLF, three associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), three controls) before and after PHx.
- Quantitative mass spectrometry was employed to analyze the proteomic content of isolated EVs.
- Super-SILAC (Stable Isotope Labeling by Amino acid in Cell culture) mix was used for precise protein quantification.
Main Results:
- A total of 2625 proteins were identified and 2570 quantified in plasma EVs from PHx patients.
- Significant differences in EV protein expression were observed between PHLF and non-PHLF groups, as well as between PHLF and ALPPS groups.
- The EV proteomic signature in PHLF patients indicated dysregulation in protein translation, proteostasis, vesicle biogenesis, extracellular matrix remodeling, and metabolic/cell cycle pathways, detectable pre-operatively.
Conclusions:
- Longitudinal proteomic analysis of plasma EVs reveals distinct signatures associated with PHLF in patients undergoing PHx.
- These EV proteomic signatures reflect hepatocyte and endothelial cell damage.
- The identified signatures are present before the partial hepatectomy, suggesting potential for early prediction of PHLF.
