title: Chronic kidney disease alters vascular smooth muscle cell phenotype.
abstract: Vascular access dysfunction associated with arteriovenous grafts and fistulas contributes to the morbidity and mortality of chronic kidney disease (CKD) patients receiving hemodialysis. We hypothesized that the uremic conditions associated with CKD promote a pathophysiological vascular smooth muscle cell (VSMC) phenotype that contributes to neointimal hyperplasia. We analyzed the effect of culturing human VSMC with uremic serum. Expression of VSMC contractile marker genes was reduced 50-80% in cells exposed to uremic serum and the decreased expression was accompanied by changes in histone marks. There was an increase in proliferation in cells exposed to uremic conditions, with no change in the levels of apoptosis. Interestingly, we found that uremic serum inhibited PDGF-induced migration of VSMC. Histomorphometric analysis revealed venous neointimal hyperplasia in veins from chronic kidney disease (CKD) patients prior to any surgical manipulation as compared to veins from patients with no kidney disease. We conclude that uremia associated with CKD alters VSMC phenotype in vitro and contributes to neointimal hyperplasia formation in vivo contributing to the pathogenesis of vascular access dysfunction in CKD patients.
authors.affiliation: Center for Metabolic Disease Research, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140.
authors.forename: M Alexandra
authors.initials: MA
authors.lastname: Monroy
authors.affiliation: Center for Metabolic Disease Research, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Fang
authors.affiliation: Center for Metabolic Disease Research, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Center for Metabolic Disease Research, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140.
authors.forename: Lucas
authors.initials: L
authors.lastname: Ferrer
authors.affiliation: Center for Metabolic Disease Research, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Birkenbach
authors.affiliation: Center for Metabolic Disease Research, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140.
authors.forename: Iris J
authors.initials: IJ
authors.lastname: Lee
authors.affiliation: Center for Metabolic Disease Research, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Center for Metabolic Disease Research, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Center for Metabolic Disease Research, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Choi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D007676:Kidney Failure, Chronic / Q000473:pathology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D019311:Staurosporine / Q000494:pharmacology; D014511:Uremia / Q000097:blood; D062666:Vascular Access Devices
chemical_list: D015415:Biomarkers; D019311:Staurosporine