Endothelial Surface Layer Degradation by Chronic Hyaluronidase Infusion Induces Proteinuria in Apolipoprotein E-Deficient Mice

Marijn C. Meuwese*, Lysette N. Broekhuizen, Mayella Kuikhoven, Sylvia Heeneman, Esther Lutgens, Marion J. J. Gijbels, Max Nieuwdorp, Carine J. Peutz, Erik S. G. Stroes, Hans Vink, Bernard M. van den Berg

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

35 Citations (Web of Science)

Abstract

Objective: Functional studies show that disruption of endothelial surface layer (ESL) is accompanied by enhanced sensitivity of the vasculature towards atherogenic stimuli. However, relevance of ESL disruption as causal mechanism for vascular dysfunction remains to be demonstrated. We examined if loss of ESL through enzymatic degradation would affect vascular barrier properties in an atherogenic model. Methods: Eight week old male apolipoprotein E deficient mice on Western-type diet for 10 weeks received continuous active or heat-inactivated hyaluronidase (10 U/hr, i.v.) through an osmotic minipump during 4 weeks. Blood chemistry and anatomic changes in both macrovasculature and kidneys were examined. Results: Infusion with active hyaluronidase resulted in decreased ESL (0.32+/-0.22 mL) and plasma volume (1.03+/-0.18 mL) compared to inactivated hyaluronidase (0.52+/-0.29 mL and 1.28+/-0.08 mL, p
Original languageEnglish
Pages (from-to)7
JournalPLOS ONE
Volume5
Issue number12
DOIs
Publication statusPublished - 8 Dec 2010

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