Endothelial nitric oxide synthase prevents heparanase induction and the development of proteinuria

Marjolein Garsen, Angelique L. Rops, Jinhua Li, Katrien Van Beneden, Christiane Van Den Branden, Jo H.M. Berden, Ton J. Rabelink, Johan Van Der Vlag

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Endothelial nitric oxide synthase (eNOS) deficiency exacerbates proteinuria and renal injury in several glomerular diseases, but the underlying mechanism is not fully understood. We recently showed that heparanase is essential for the development of experimental diabetic nephropathy and glomerulonephritis, and hypothesize that heparanase expression is regulated by eNOS. Here, we demonstrate that induction of adriamycin nephropathy (AN) in C57BL/6 eNOS-deficient mice leads to an increased glomerular heparanase expression accompanied with overt proteinuria, which was not observed in the AN-resistant wild type counterpart. In vitro, the eNOS inhibitor asymmetric dimethylarginine (ADMA) induced heparanase expression in cultured mouse glomerular endothelial cells. Moreover, ADMA enhanced transendothelial albumin passage in a heparanase-dependent manner. We conclude that eNOS prevents heparanase induction and the development of proteinuria.

Original languageEnglish
Article numbere0160894
Number of pages8
JournalPLoS ONE
Volume11
Issue number8
DOIs
Publication statusPublished - 1 Aug 2016

Cite this

Garsen, M., Rops, A. L., Li, J., Van Beneden, K., Van Den Branden, C., Berden, J. H. M., ... Van Der Vlag, J. (2016). Endothelial nitric oxide synthase prevents heparanase induction and the development of proteinuria. PLoS ONE, 11(8), [e0160894]. https://doi.org/10.1371/journal.pone.0160894
Garsen, Marjolein ; Rops, Angelique L. ; Li, Jinhua ; Van Beneden, Katrien ; Van Den Branden, Christiane ; Berden, Jo H.M. ; Rabelink, Ton J. ; Van Der Vlag, Johan. / Endothelial nitric oxide synthase prevents heparanase induction and the development of proteinuria. In: PLoS ONE. 2016 ; Vol. 11, No. 8.
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Garsen, M, Rops, AL, Li, J, Van Beneden, K, Van Den Branden, C, Berden, JHM, Rabelink, TJ & Van Der Vlag, J 2016, 'Endothelial nitric oxide synthase prevents heparanase induction and the development of proteinuria' PLoS ONE, vol. 11, no. 8, e0160894. https://doi.org/10.1371/journal.pone.0160894

Endothelial nitric oxide synthase prevents heparanase induction and the development of proteinuria. / Garsen, Marjolein; Rops, Angelique L.; Li, Jinhua; Van Beneden, Katrien; Van Den Branden, Christiane; Berden, Jo H.M.; Rabelink, Ton J.; Van Der Vlag, Johan.

In: PLoS ONE, Vol. 11, No. 8, e0160894, 01.08.2016.

Research output: Contribution to journalArticleResearchpeer-review

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Garsen M, Rops AL, Li J, Van Beneden K, Van Den Branden C, Berden JHM et al. Endothelial nitric oxide synthase prevents heparanase induction and the development of proteinuria. PLoS ONE. 2016 Aug 1;11(8). e0160894. https://doi.org/10.1371/journal.pone.0160894