{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T09:53:42Z","timestamp":1784886822929,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01DK122813"],"award-info":[{"award-number":["R01DK122813"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P-32064"],"award-info":[{"award-number":["P-32064"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P-34783"],"award-info":[{"award-number":["P-34783"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Austrian Science Fund (FWF)","award":["R01DK122813"],"award-info":[{"award-number":["R01DK122813"]}]},{"name":"Austrian Science Fund (FWF)","award":["P-32064"],"award-info":[{"award-number":["P-32064"]}]},{"name":"Austrian Science Fund (FWF)","award":["P-34783"],"award-info":[{"award-number":["P-34783"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Post-hepatectomy liver failure (PHLF) remains a significant risk for patients undergoing partial hepatectomy (PHx). Reliable prognostic markers and treatments to enhance liver regeneration are lacking. Plasma nanoparticles, including lipoproteins, exosomes, and extracellular vesicles (EVs), can reflect systemic and tissue-wide proteostasis and stress, potentially aiding liver regeneration. However, their role in PHLF is still unknown. Methods: Our study included nine patients with hepatocellular carcinoma (HCC) undergoing PHx: three patients with PHLF, three patients undergoing the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure, and three matched controls without complications after PHx. Patient plasma was collected before PHx as well as 1 and 5 days after. EVs were isolated by ultracentrifugation, and extracted proteins were subjected to quantitative mass spectrometry using a super-SILAC mix prepared from primary and cancer cell lines. Results: We identified 2625 and quantified 2570 proteins in the EVs of PHx patients. Among these, 53 proteins were significantly upregulated and 32 were downregulated in patients with PHLF compared to those without PHLF. Furthermore, 110 proteins were upregulated and 78 were downregulated in PHLF patients compared to those undergoing ALPPS. The EV proteomic signature in PHLF indicates significant disruptions in protein translation, proteostasis, and intracellular vesicle biogenesis, as well as alterations in proteins involved in extracellular matrix (ECM) remodelling and the metabolic and cell cycle pathways, already present before PHx. Conclusions: Longitudinal proteomic analysis of the EVs circulating in the plasma of human patients undergoing PHx uncovers proteomic signatures associated with PHLF, which reflect dying hepatocytes and endothelial cells and were already present before PHx.<\/jats:p>","DOI":"10.3390\/ijms251910685","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T03:26:36Z","timestamp":1728012396000},"page":"10685","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["SILAC-Based Characterization of Plasma-Derived Extracellular Vesicles in Patients Undergoing Partial Hepatectomy"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8380-9555","authenticated-orcid":false,"given":"Ulrike","family":"Resch","sequence":"first","affiliation":[{"name":"Department of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria"},{"name":"Cluster of Excellence\/Cellular Stress Responses in Aging\/Associated Diseases (CECAD), Proteomics Core Facilities, University of Cologne, Joseph-Stelzmann Strasse 26, D-50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4055-3841","authenticated-orcid":false,"given":"Hubert","family":"Hackl","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innrain 80, A-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6700-9163","authenticated-orcid":false,"given":"David","family":"Pereyra","sequence":"additional","affiliation":[{"name":"Department of Surgery, General Hospital, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, A-1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Santol","sequence":"additional","affiliation":[{"name":"Department of Surgery, General Hospital, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, A-1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Brunnthaler","sequence":"additional","affiliation":[{"name":"Department of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Probst","sequence":"additional","affiliation":[{"name":"Department of Surgery, General Hospital, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, A-1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Sofie","family":"Jankoschek","sequence":"additional","affiliation":[{"name":"Department of Surgery, General Hospital, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, A-1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Aiad","sequence":"additional","affiliation":[{"name":"Department of Surgery, General Hospital, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, A-1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Nolte","sequence":"additional","affiliation":[{"name":"Cluster of Excellence\/Cellular Stress Responses in Aging\/Associated Diseases (CECAD), Proteomics Core Facilities, University of Cologne, Joseph-Stelzmann Strasse 26, D-50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Krueger","sequence":"additional","affiliation":[{"name":"Cluster of Excellence\/Cellular Stress Responses in Aging\/Associated Diseases (CECAD), Proteomics Core Facilities, University of Cologne, Joseph-Stelzmann Strasse 26, D-50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Starlinger","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innrain 80, A-6020 Innsbruck, Austria"},{"name":"Department of Surgery, General Hospital, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, A-1090 Vienna, Austria"},{"name":"Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN 55902, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5670-5910","authenticated-orcid":false,"given":"Alice","family":"Assinger","sequence":"additional","affiliation":[{"name":"Department of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, 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