PMID- 29423208
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220311
IS  - 2048-8505 (Print)
IS  - 2048-8513 (Electronic)
IS  - 2048-8505 (Linking)
VI  - 11
IP  - 1
DP  - 2018 Feb
TI  - Sevelamer reduces endothelial inflammatory response to advanced glycation end 
      products.
PG  - 89-98
LID - 10.1093/ckj/sfx074 [doi]
AB  - BACKGROUND: Advanced glycation end products (AGEs) have been related to the 
      pathogenesis of cardiovascular diseases (CVD), chronic kidney disease (CKD) and 
      diabetes mellitus. We sought to investigate the binding capacity of sevelamer to 
      both AGEs and uremic serum in vitro and then test this pharmaceutical effect as a 
      potential vascular anti-inflammatory strategy. METHODS: AGEs were prepared by 
      albumin glycation and characterized by absorbance and electrophoresis. Human 
      endothelial cells were incubated in culture media containing AGEs and uremic 
      serum with or without sevelamer. Receptor for advanced glycation end product 
      (RAGE) expression was evaluated through immunocytochemistry and western blot to 
      explore the interactions between AGEs and the endothelium. Inflammatory and 
      endothelial dysfunction biomarkers, such as interleukin 6 (IL-6) and IL-8, 
      monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 
      (PAI-1) and serum amyloid A (SAA) were also measured in cell supernatant. The 
      chemotactic property of the supernatant was evaluated. RESULTS: AGEs 
      significantly induced the expression of RAGE, inflammatory and endothelial 
      activation biomarkers [IL-6, (P < 0.005); IL-8, MCP-1, PAI-1 and SAA (P < 0.001)] 
      and monocyte chemotaxis as compared with controls. In addition, AGEs increased 
      the levels of inflammatory biomarkers, which were observed after 6 h of 
      endothelial cell incubation with uremic serum [IL-6 (P < 0.001) IL-8, MCP-1 and 
      PAI-1 (P < 0.05)]. On the other hand, after 6 h of endothelial cell treatment 
      with sevelamer, RAGE expression (P < 0.05) and levels of inflammatory biomarkers 
      [IL-6 and IL-8 (P < 0.001), MCP-1 (P < 0.01), PAI-1 and SAA (P < 0.005)] 
      significantly decreased compared with the AGEs/uremic serum treatment alone. 
      CONCLUSIONS: Sevelamer decreased both endothelial expression of RAGE and 
      endothelial dysfunction biomarkers, induced by AGEs, and uremic serum. Further 
      studies are necessary for a better understanding of the potential protective role 
      of sevelamer on uremic serum and AGEs-mediated endothelial dysfunction.
FAU - Gregorio, Paulo C
AU  - Gregorio PC
AD  - Experimental Nephrology Laboratory, Basic Pathology Department, Universidade 
      Federal do Parana, Curitiba, Parana, Brazil.
FAU - Favretto, Giane
AU  - Favretto G
AD  - Experimental Nephrology Laboratory, Basic Pathology Department, Universidade 
      Federal do Parana, Curitiba, Parana, Brazil.
FAU - Sassaki, Guilherme L
AU  - Sassaki GL
AD  - Biochemistry Department, Universidade Federal do Parana, Curitiba, Parana, 
      Brazil.
FAU - Cunha, Regiane S
AU  - Cunha RS
AD  - Experimental Nephrology Laboratory, Basic Pathology Department, Universidade 
      Federal do Parana, Curitiba, Parana, Brazil.
FAU - Becker-Finco, Alessandra
AU  - Becker-Finco A
AD  - Experimental Nephrology Laboratory, Basic Pathology Department, Universidade 
      Federal do Parana, Curitiba, Parana, Brazil.
FAU - Pecoits-Filho, Roberto
AU  - Pecoits-Filho R
AD  - School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, Parana, 
      Brazil.
FAU - Souza, Wesley M
AU  - Souza WM
AD  - Pharmacy Departament, Universidade Federal do Parana, Curitiba, Parana, Brazil.
FAU - Barreto, Fellype C
AU  - Barreto FC
AD  - Department of Internal Medicine, Division of Nephrology, Universidade Federal do 
      Parana, Curitiba, Parana, Brazil.
FAU - Stinghen, Andrea E M
AU  - Stinghen AEM
AD  - Experimental Nephrology Laboratory, Basic Pathology Department, Universidade 
      Federal do Parana, Curitiba, Parana, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20170905
PL  - England
TA  - Clin Kidney J
JT  - Clinical kidney journal
JID - 101579321
PMC - PMC5798142
OTO - NOTNLM
OT  - AGEs
OT  - chronic kidney disease
OT  - endothelial dysfunction
OT  - inflammation
OT  - sevelamer
OT  - uremic serum
EDAT- 2018/02/10 06:00
MHDA- 2018/02/10 06:01
PMCR- 2017/09/05
CRDT- 2018/02/10 06:00
PHST- 2017/03/04 00:00 [received]
PHST- 2017/06/02 00:00 [accepted]
PHST- 2018/02/10 06:00 [entrez]
PHST- 2018/02/10 06:00 [pubmed]
PHST- 2018/02/10 06:01 [medline]
PHST- 2017/09/05 00:00 [pmc-release]
AID - sfx074 [pii]
AID - 10.1093/ckj/sfx074 [doi]
PST - ppublish
SO  - Clin Kidney J. 2018 Feb;11(1):89-98. doi: 10.1093/ckj/sfx074. Epub 2017 Sep 5.