title: Hepatic syndecan-1 changes associate with dyslipidemia after renal transplantation.
abstract: Syndecan-1 is a transmembrane heparan sulfate (HS) proteoglycan present on hepatocytes and involved in uptake of triglyceride-rich lipoproteins via its HS polysaccharide side chains. We hypothesized that altered hepatic syndecan-1 metabolism could be involved in dyslipidemia related to renal transplantation. In a rat renal transplantation model elevated plasma triglycerides were associated with fivefold increased expression of hepatic syndecan-1 mRNA (p < 0.01), but not protein. Expression of syndecan-1 sheddases (ADAM17, MMP9) and heparanase was significantly up-regulated after renal transplantation (all p < 0.05). Profiling of HS side chains revealed loss of hepatic HS upon renal transplantation accompanied by significant decreased functional capacity for VLDL binding (p = 0.02). In a human renal transplantation cohort (n = 510), plasma levels of shed syndecan-1 were measured. Multivariate analysis showed plasma syndecan-1 to be independently associated with triglycerides (p < 0.0001) and inversely with HDL cholesterol (p < 0.0001). Last, we show a physical association of syndecan-1 to HDL from renal transplant recipients (RTRs), but not to HDL from healthy controls. Our data suggest that after renal transplantation loss of hepatic HS together with increased syndecan-1 shedding hampers lipoprotein binding and uptake by the liver contributing to dyslipidemia. Our data open perspectives toward improvement of lipid profiles by targeted inhibition of syndecan-1 catabolism in renal transplantation.
authors.affiliation: Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Adepu
authors.forename: K
authors.initials: K
authors.lastname: Katta
authors.forename: U J F
authors.initials: UJ
authors.lastname: Tietge
authors.forename: A J
authors.initials: AJ
authors.lastname: Kwakernaak
authors.forename: W
authors.initials: W
authors.lastname: Dam
authors.forename: H
authors.initials: H
authors.lastname: van Goor
authors.forename: R P F
authors.initials: RP
authors.lastname: Dullaart
authors.forename: G J
authors.initials: GJ
authors.lastname: Navis
authors.forename: S J L
authors.initials: SJ
authors.lastname: Bakker
authors.forename: J
authors.initials: J
authors.lastname: van den Born
mesh_terms: D000818:Animals; D050171:Dyslipidemias / Q000378:metabolism*; D005260:Female; D016030:Kidney Transplantation; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D053668:Syndecan-1 / Q000378:metabolism*
chemical_list: C508241:SDC1 protein, human; D053668:Syndecan-1
keywords: Basic (laboratory) research/science; hyperlipidemia; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; liver (native) function/dysfunction; pathology/histopathology; translational research/science