dc.contributor.author | Engberink, Rik H. G. Olde | |
dc.contributor.author | de Vos, Judith | |
dc.contributor.author | van Weert, Angela | |
dc.contributor.author | Zhang, Yahua | |
dc.contributor.author | van Vlies, Naomi | |
dc.contributor.author | van den Born, Bert-Jan H. | |
dc.contributor.author | Titze, Jens M.) | |
dc.contributor.author | van Bavel, Ed | |
dc.contributor.author | Vogt, Liffert | |
dc.date.accessioned | 2020-08-24T21:31:56Z | |
dc.date.available | 2020-08-24T21:31:56Z | |
dc.date.issued | 2019-07-31 | |
dc.identifier.citation | Olde Engberink RHG, de Vos J, van Weert A, Zhang Y, van Vlies N, van den Born B-JH, et al. (2019) Abnormal sodium and water homeostasis in mice with defective heparan sulfate polymerization. PLoS ONE 14(7): e0220333. https://doi.org/10.1371/journal.pone.0220333 | en_US |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/1803/15569 | |
dc.description.abstract | Glycosaminoglycans in the skin interstitium and endothelial surface layer have been shown to be involved in local sodium accumulation without commensurate water retention. Dysfunction of heparan sulfate glycosaminoglycans may therefore disrupt sodium and water homeostasis. In this study, we investigated the effects of combined heterozygous loss of heparan sulfate polymerization genes (exostosin glycosyltransferase 1 and 2; Ext1(+/-)Ext2(+/-)) on sodium and water homeostasis. Sodium storage capacity was decreased in Ext1(+/-)Ext2(+/-) mice as reflected by a 77% reduction in endothelial surface layer thickness and a lower skin sodium-to-glycosaminoglycan ratio. Also, these mice were characterized by a higher heart rate, increased fluid intake, increased plasma osmolality and a decreased skin water and sodium content, suggesting volume depletion. Upon chronic high sodium intake, the initial volume depletion was restored but no blood pressure increase was observed. Acute hypertonic saline infusion resulted in a distinct blood pressure response: we observed a significant 15% decrease in control mice whereas blood pressure did not change in Ext1(+/-)Ext2(+/-) mice. This differential blood pressure response may be explained by the reduced capacity for sodium storage and/or the impaired vasodilation response, as measured by wire myography, which was observed in Ext1(+/-)Ext2(+/-) mice. Together, these data demonstrate that defective heparan sulfate glycosaminoglycan synthesis leads to abnormal sodium and water homeostasis and an abnormal response to sodium loading, most likely caused by inadequate capacity for local sodium storage. | en_US |
dc.description.sponsorship | L.V. was supported by Kolff Grant KJPB 11.22 from the Dutch Kidney Foundation (www.nierstichting.nl). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The authors would like to thank Jurgen van Teeffelen and Hanneke Cobelens (Maastricht University, Maastricht) for providing training in cremaster surgery, Beatrice Bedussi (AMC, Amsterdam) for her contributions to the carotid artery surgery and Tom Wagemans (AMC, Amsterdam) for his help with the HPLC MS/MS measurements. L.V. was supported by Kolff Grant KJPB 11.22 from the Dutch Kidney Foundation. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | PLoS One | en_US |
dc.rights | Copyright: © 2019 Olde Engberink et al. This is an
open access article distributed under the terms of
the Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited. | |
dc.source.uri | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220333 | |
dc.title | Abnormal sodium and water homeostasis in mice with defective heparan sulfate polymerization | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1371/journal.pone.0220333 | |