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Metalloproteinase-9 mRNA expression in monocytes from patients with chronic renal failure
I Ebihara1, T Nakamura, Y Tomino
1Department of Medicine, Koto Hospital, Tokyo, Japan.
Abstract:
Long-term dialysis patients suffer from various complications including atherosclerosis. It has been suggested that metalloproteinases (MMPs) contribute to vascular remodeling during the development and progression of human atherosclerosis. Activated human monocytes have been demonstrated to secrete MMPs. In the present study, we measured levels of MMP mRNA in peripheral blood monocytes obtained from patients on continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD) and chronic-renal-failure patients not undergoing dialysis. Twenty patients with chronic renal failure were not undergoing dialysis, 20 patients were on CAPD, 40 patients were on chronic HD and 20 healthy volunteers served as controls. We used cDNA probes encoding for MMP-1, MMP-2, MMP-3 and MMP-9 and glyceraldehyde phosphate dehydrogenase. Higher levels of MMP-9 mRNA in the peripheral blood monocytes were observed in HD patients than in CAPD patients, undialyzed chronic renal failure patients or healthy controls. MMP-9 mRNA levels at the end of HD were not significantly higher than those at the start of HD. MMP-9 mRNA levels from HD patients did not differ among the types of membranes. We could detect minimal MMP-1, MMP-2 and MMP-3 mRNA expression in monocytes from all groups. Serum gelatinase activity was detectable in all samples; however, no significant differences existed among the groups. In summary, MMP-9 mRNA expression is enhanced in monocytes from HD and CAPD patients, and the enhancement may be, in part, associated with cardiovascular complications, including atherosclerosis, in dialysis patients. This increase in monocyte MMP-9 mRNA levels is lower in CAPD patients that it is in HD patients.
Insights
Dialysis patients show increased metalloproteinase-9 (MMP-9) mRNA in monocytes, a factor potentially linked to atherosclerosis. Hemodialysis patients exhibit higher levels than peritoneal dialysis patients.
Area of Science:
- Nephrology
- Cardiovascular Science
- Molecular Biology
Background:
- Long-term dialysis patients face complications like atherosclerosis.
- Metalloproteinases (MMPs), particularly MMP-9, are implicated in vascular remodeling and atherosclerosis.
- Monocytes are known to secrete MMPs upon activation.
Purpose of the Study:
- To quantify messenger RNA (mRNA) levels of MMP-1, MMP-2, MMP-3, and MMP-9 in peripheral blood monocytes.
- To compare MMP mRNA levels between patients undergoing hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), chronic renal failure patients not on dialysis, and healthy controls.
Main Methods:
- Monocyte isolation from peripheral blood of 20 undialyzed chronic renal failure patients, 20 CAPD patients, 40 HD patients, and 20 healthy controls.
- Quantification of MMP-1, MMP-2, MMP-3, and MMP-9 mRNA using cDNA probes and glyceraldehyde phosphate dehydrogenase as a reference.
- Measurement of serum gelatinase activity.
Main Results:
- Significantly higher MMP-9 mRNA levels were found in monocytes of HD patients compared to CAPD, undialyzed, and control groups.
- MMP-9 mRNA levels in HD patients did not change significantly during dialysis or vary with membrane type.
- Minimal expression of MMP-1, MMP-2, and MMP-3 mRNA was detected across all groups.
- Serum gelatinase activity showed no significant differences among the groups.
Conclusions:
- Enhanced MMP-9 mRNA expression in monocytes of dialysis patients (HD and CAPD) may contribute to cardiovascular complications like atherosclerosis.
- The increase in monocyte MMP-9 mRNA levels is less pronounced in CAPD patients than in HD patients.