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Three monocyte-related determinants of atherosclerosis in haemodialysis
S H Jacobson1, P Thylén, J Lundahl
1Departments of Nephrology, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden.
Insights
Hemodialysis patients show increased monocyte activity and elevated levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and monocyte chemotactic protein-1 (MCP-1). These changes suggest a role in atherosclerosis development for patients undergoing dialysis.
Area of Science:
- Nephrology
- Immunology
- Cardiovascular Medicine
Background:
- Monocyte-related inflammatory mediators are implicated in atherosclerosis.
- Hemodialysis can alter monocyte adhesion molecule expression.
- Soluble vascular cell adhesion molecule-1 (sVCAM-1) and monocyte chemotactic protein-1 (MCP-1) are key inflammatory markers.
Purpose of the Study:
- To investigate monocyte count, CD11b/CD18 expression, MCP-1, and sVCAM-1 in hemodialysis patients.
- To compare these markers between patients on different dialysis membranes and healthy subjects.
- To explore correlations between these markers and dialysis treatment.
Main Methods:
- Studied monocyte count, CD11b/CD18 expression, MCP-1, and sVCAM-1 in 9 hemodialysis patients (18 treatments) and 18 healthy controls.
- Measurements were taken at multiple time points before, during, and after hemodialysis.
- Statistical analysis included comparisons between groups and correlation analyses.
Main Results:
- Monocyte CD11b/CD18 expression significantly increased during and after dialysis for both membranes.
- sVCAM-1 and MCP-1 concentrations were elevated in hemodialysis patients compared to controls at all time points.
- Significant correlations were found between CD11b/CD18 expression and sVCAM-1/MCP-1 levels, and between MCP-1 and sVCAM-1.
Conclusions:
- Hemodialysis patients exhibit increased systemic monocyte chemotactic activity and altered monocyte CD11b/CD18 expression.
- Elevated sVCAM-1 and MCP-1 concentrations are present in hemodialysis patients.
- Further research is required to determine the role of these abnormalities in hemodialysis-related atherosclerosis.
Background:
It has been suggested that monocyte-related inflammatory mediators play a role in atherosclerosis. Haemodialysis induces phenotypic changes in adhesion molecule expression on monocytes. Soluble vascular cell adhesion molecule-1 (sVCAM-1), an adhesion molecule involved in monocyte recruitment, has been proposed to correlate with the extent of atherosclerosis in humans. Monocyte chemotactic protein-1 (MCP-1) functions as a monocyte-specific chemoattractant.
Methods:
We studied monocyte count, CD11b/CD18 expression on monocytes, MCP-1, and sVCAM-1 in nine patients on either cuprophane or polysulphone haemodialysis (n=18 treatments) at times 0 (before haemodialysis), 3 h (end of haemodialysis), 4, 6, 8 and 24 h after start of treatment, as well as in 18 healthy subjects.
Results:
Monocyte CD11b/CD18 expression increased with both membranes (P:<0.001) during and after dialysis compared to before treatment. The concentrations of sVCAM-1 and MCP-1 were higher in patients compared to those in controls both before, during and after haemodialysis (P:<0.001 at all time points). There were correlations between the expression of CD11b/CD18 on monocytes and the interdialytic concentrations of sVCAM-1 (r=0.76, P:<0.001) and MCP-1 (r=0.54, P:<0.05) and between MCP-1 and sVCAM-1 before and after haemodialysis (P:<0.05).
Conclusion:
Patients on haemodialysis have an increased systemic chemotactic activity for monocytes, unphysiological phenotypic alterations in CD11b/ CD18 expression during and after dialysis, and increased sVCAM-1 and MCP-1 concentrations. Prospective studies are needed to establish the role of these abnormalities in the pathogenesis of atherosclerosis in haemodialysis patients.