PMID- 19147993
OWN - NLM
STAT- MEDLINE
DCOM- 20091207
LR  - 20220311
IS  - 1660-2110 (Electronic)
IS  - 1660-2110 (Linking)
VI  - 111
IP  - 2
DP  - 2009
TI  - Increased plasma and endothelial cell expression of chemokines and adhesion 
      molecules in chronic kidney disease.
PG  - c117-26
LID - 10.1159/000191205 [doi]
AB  - Chemokines and adhesion molecules are involved in early events of atherogenesis. 
      In the present study, we investigated the effects of the uremic milieu on the 
      expression of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), 
      soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion 
      molecule-1 (sICAM-1) and their relationship to cardiovascular status. Plasma 
      samples were obtained from patients in different stages of chronic kidney disease 
      (CKD). Cardiovascular status was evaluated by intima-media thickness and 
      endothelial dysfunction by flow mediation dilatation and proteinuria. In vitro 
      studies were performed using human umbilical endothelial cells exposed to uremic 
      plasma or plasma from healthy subjects. MCP-1, IL-8, sVCAM-1 and sICAM-1 levels 
      in plasma and in supernatant were analyzed by enzyme-linked immunosorbent assay. 
      The population consisted of 73 (mean age 57 years; 48% males) CKD patients with 
      glomerular filtration rate (GFR) of 37 +/- 2 ml/min. MCP-1 and sVCAM-1 plasma 
      levels were negatively correlated with GFR (rho = -0.40, p < 0.0005 and rho = 
      -0.42, p < 0.0005, respectively). Fibrinogen was positively correlated with 
      MCP-1, sICAM-1 and sVCAM-1 (rho = 0.33, p < 0.005, rho = 0.32, p < 0.05 and rho = 
      0.25, p < 0.05, respectively) and ultra-high-sensitivity C-reactive protein was 
      positively correlated with sICAM-1 (rho = 0.25, p < 0.0005). Plasma IL-8 had a 
      significant positive correlation with proteinuria (rho = 0.31, p < 0.01). There 
      was a time- and CKD-stage-dependent MCP-1, IL-8 and sVCAM-1 endothelial 
      expression (p < 0.05). In summary, plasma levels of markers of endothelial cell 
      activation (MCP-1 and sVCAM-1) are increased in more advanced CKD. Exposure of 
      endothelial cells to uremic plasma results in a time- and CKD-stage-dependent 
      increased expression of MCP-1, IL-8 and sVCAM-1, suggesting a link between 
      vascular activation, systemic inflammation and uremic toxicity. Future studies 
      are necessary to investigate whether these biomarkers add predictive value in 
      comparison to the previously described ones. Also, endothelial response to uremic 
      toxicity should be viewed as a potential target for intervention in order to 
      reduce morbidity and mortality in CKD-related cardiovascular disease.
CI  - Copyright 2009 S. Karger AG, Basel.
FAU - Stinghen, A E M
AU  - Stinghen AE
AD  - Center for Health and Biological Sciences, Pontificia Universidade Catolica do 
      Parana, Curitiba, Brazil.
FAU - Goncalves, S M
AU  - Goncalves SM
FAU - Martines, E G
AU  - Martines EG
FAU - Nakao, L S
AU  - Nakao LS
FAU - Riella, M C
AU  - Riella MC
FAU - Aita, C A
AU  - Aita CA
FAU - Pecoits-Filho, R
AU  - Pecoits-Filho R
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090116
PL  - Switzerland
TA  - Nephron Clin Pract
JT  - Nephron. Clinical practice
JID - 101159763
RN  - 0 (Biomarkers)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokines)
SB  - IM
MH  - Biomarkers/blood
MH  - Cell Adhesion Molecules/*biosynthesis/*blood
MH  - Cells, Cultured
MH  - Chemokines/*biosynthesis/*blood
MH  - Endothelial Cells/*metabolism
MH  - Female
MH  - Gene Expression Regulation/*physiology
MH  - Humans
MH  - Kidney Failure, Chronic/*blood
MH  - Male
MH  - Middle Aged
EDAT- 2009/01/17 09:00
MHDA- 2009/12/16 06:00
CRDT- 2009/01/17 09:00
PHST- 2008/02/26 00:00 [received]
PHST- 2008/09/04 00:00 [accepted]
PHST- 2009/01/17 09:00 [entrez]
PHST- 2009/01/17 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - 000191205 [pii]
AID - 10.1159/000191205 [doi]
PST - ppublish
SO  - Nephron Clin Pract. 2009;111(2):c117-26. doi: 10.1159/000191205. Epub 2009 Jan 
      16.