High sodium diet converts renal proteoglycans into pro-inflammatory mediators in ratsReportar como inadecuado




High sodium diet converts renal proteoglycans into pro-inflammatory mediators in rats - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Background

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.

Methods

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.

Results

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.

Conclusion

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.



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

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados