title: The soluble VEGF receptor sFlt1 contributes to endothelial dysfunction in CKD.
abstract: Endothelial dysfunction contributes to the increased cardiovascular risk that accompanies CKD. We hypothesized that the soluble VEGF receptor 1 (sFlt-1), a VEGF antagonist, plays a role in endothelial dysfunction and decreased angiogenesis in CKD. We enrolled 130 patients with CKD stages 3 to 5 and 56 age- and gender-matched control patients. Plasma sFlt-1 levels were higher in patients with CKD and, after multivariate regression analyses, exclusively associated with renal function and levels of vWF, a marker of endothelial dysfunction. Compared with serum from control patients, both recombinant sFlt-1 and serum from patients with CKD had antiangiogenic activity in the chick chorioallantoic membrane (CAM) assay, induced endothelial cell apoptosis in vitro, and decreased nitric oxide generation in two different endothelial cell lines. Pretreating the sera with an antibody against sFlt-1 abrogated all of these effects. Furthermore, we observed increased sFlt1 levels in 5/6-nephrectomized rats compared with sham-operated animals. Finally, using real-time PCR and ELISA, we identified monocytes as a possible source of increased sFlt-1 in patients with CKD. Our findings show that excess sFlt-1 associates with endothelial dysfunction in CKD and suggest that increased sFlt-1 may predict cardiovascular risk in CKD.
authors.affiliation: Department of Internal Medicine D, University Clinics Münster, Münster, Germany.
authors.forename: Giovana S
authors.initials: GS
authors.lastname: Di Marco
authors.forename: Stefan
authors.initials: S
authors.lastname: Reuter
authors.forename: Uta
authors.initials: U
authors.lastname: Hillebrand
authors.forename: Susanne
authors.initials: S
authors.lastname: Amler
authors.forename: Maximilian
authors.initials: M
authors.lastname: König
authors.forename: Etienne
authors.initials: E
authors.lastname: Larger
authors.forename: Hans
authors.initials: H
authors.lastname: Oberleithner
authors.forename: Eva
authors.initials: E
authors.lastname: Brand
authors.forename: Hermann
authors.initials: H
authors.lastname: Pavenstädt
authors.forename: Marcus
authors.initials: M
authors.lastname: Brand
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D002908:Chronic Disease; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry; D009569:Nitric Oxide / Q000096:biosynthesis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1