High sodium diet converts renal proteoglycans into pro-inflammatory mediators in ratsReport as inadecuate

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High dietary sodium aggravates renal disease by affecting blood pressure and by its recently shown pro-inflammatory and pro-fibrotic effects. Moreover, pro-inflammatory modification of renal heparan sulfate HS can induce tissue remodeling. We aim to investigate if high sodium intake in normotensive rats converts renal HS into a pro-inflammatory phenotype, able to bind more sodium and orchestrate inflammation, fibrosis and lymphangiogenesis.


Wistar rats received a normal diet for 4 weeks, or 8% NaCl diet for 2 or 4 weeks. Blood pressure was monitored, and plasma, urine and tissue collected. Tissue sodium was measured by flame spectroscopy. Renal HS and tubulo-interstitial remodeling were studied by biochemical, immunohistochemical and qRT-PCR approaches.


High sodium rats showed a transient increase in blood pressure week 1; p<0.01 and increased sodium excretion p<0.05 at 2 and 4 weeks compared to controls. Tubulo-interstitial T-cells, myofibroblasts and mRNA levels of VCAM1, TGF-β1 and collagen type III significantly increased after 4 weeks all p<0.05. There was a trend for increased macrophage infiltration and lymphangiogenesis both p = 0.07. Despite increased dermal sodium over time p<0.05, renal concentrations remained stable. Renal HS of high sodium rats showed increased sulfation p = 0.05, increased L-selectin binding to HS p<0,05, and a reduction of sulfation-sensitive anti-HS mAbs JM403 p<0.001 and 10E4 p<0.01. Hyaluronan expression increased under high salt conditions p<0.01 without significant changes in the chondroitin sulfate proteoglycan versican. Statistical analyses showed that sodium-induced tissue remodeling responses partly correlated with observed HS changes.


We show that high salt intake by healthy normotensive rats convert renal HS into high sulfated pro-inflammatory glycans involved in tissue remodeling events, but not in increased sodium storage.

Author: Ryanne S. Hijmans , Pragyi Shrestha, Kwaku A. Sarpong, Saleh Yazdani, Rana el Masri, Wilhelmina H. A. de Jong, Gerjan Navis, Roma

Source: http://plos.srce.hr/


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