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- W2413537883 abstract "We appreciate the critical letter by Lisman and Porte following our recently published article. Indeed, we only investigated liver function, not liver growth. However, the two processes are tightly linked, and functional liver regeneration is clinically more relevant than volumetric liver growth. We agree with the authors that vascular endothelial growth factor (VEGF) not exclusively derives from platelets, which we also stated in our article.1 However, platelet-derived VEGF provides a rapidly available source of VEGF. In the article cited by the authors, Shimizu et al. reported that VEGF messenger RNA levels of isolated rat hepatocytes increase only 24 hours after partial hepatectomy, with a gradual increase of VEGF protein levels peaking at 72 hours.2 Accordingly, the increase in circulating VEGF in the liver vein, which we observed 2 hours after liver resection, most likely represents release of a preformed pool and not de novo synthesized hepatocyte-derived VEGF. As platelets are a major source of circulating VEGF, their contribution seems likely, specifically as platelets accumulate within the liver shortly after liver resection.1 We have now evaluated the intraplatelet VEGF content in the 37 patients within our study cohort. In line with our results on VEGF plasma levels in patients undergoing hepatectomy, we observed that platelet-stored VEGF decreased almost exclusively in patients without postoperative liver dysfunction, thereby further indicating the relevance of selective α-granule release during liver regeneration (Fig. 1). There are several differences between the results of Lisman and Porte and our study. Most importantly, they did not observe any significant changes of plasma VEGF at the onset of liver regeneration in their cohort. Furthermore, they found substantially higher VEGF levels compared to our previous reports.3 In this context, we would like to stress that plasma preparation is prone to artifacts as platelets are highly sensitive to in vitro activation.3 Therefore, it is mandatory to use the citrate, theophylline, adenosine, and dipyridamole mixture as an anticoagulant for plasma preparation and to process samples within 30 minutes at 4°C to determine platelet-derived VEGF. These technical aspects, as well as the limited number of patients, might partly explain the discrepancy between the results obtained by Lisman and Porte and our observations. Patrick Starlinger, M.D., Ph.D.1 Alice Assinger, Ph.D.2 1Department of Surgery Medical University of Vienna General Hospital Vienna, Austria 2Center of Physiology and Pharmacology Medical University of Vienna Vienna, Austria" @default.
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- W2413537883 date "2016-03-07" @default.
- W2413537883 modified "2023-09-27" @default.
- W2413537883 title "Reply" @default.
- W2413537883 cites W1933833491 @default.
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- W2413537883 doi "https://doi.org/10.1002/hep.28464" @default.
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