Adrenomedullin in peritoneal effluent expressed by peritoneal mesothelial cells
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Rika Kono1, Koichi Kanozawa, Tatsuo Shimosawa
1Division of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan, rikakono@saitama-med.ac.jp.
Background:
Adrenomedullin (AM) possesses vasodilative and cell-protective properties. Glycine combines with the C-terminal of AM to form mature, physiologically active AM (mAM). AM is reportedly induced by high glucose condition in vascular endothelial or smooth muscle cells; however, little is known on how AM is activated by amidation. To investigate the behavior of AM in patients undergoing peritoneal dialysis (PD), the concentrations of AM, mAM and CA125 were measured. The mAM to AM ratio (mAM/AM ratio) was also evaluated as a marker of amidation activity.
Methods:
Twenty patients were recruited for this study. The effluent at the time of the peritoneal equilibration test was collected and AM, mAM and CA125 concentrations were measured. The expression of AM in peritoneal mesothelial cells (PMCs) collected from effluent was also examined with an indirect immunofluorescent method.
Results:
Mean values of AM and mAM in effluent were 18.1 ± 1.6 and 4.1 ± 0.3 fmol/mL, respectively. In plasma, they were 42.6 ± 3.3 and 5.6 ± 0.6 fmol/mL, respectively. AM concentrations in effluent did not correlate with plasma AM level but correlated well with the dialysate-to-plasma ratio of creatinine (D/P ratio of creatinine). Moreover, in 7 of 20 cases, concentrations of the mAM and mAM/AM ratio in effluent were higher than in plasma. In effluent, AM concentration but not the mAM/AM ratio correlated with CA125 concentration. Immunocytological study revealed diffuse, cytoplasmic expression of AM in PMCs which were collected from effluent during PD.
Conclusion:
AM is expressed by PMCs and actively amidated in the abdominal cavity of patients undergoing PD.
Insights
Adrenomedullin (AM) is expressed by peritoneal mesothelial cells and activated by amidation within the abdominal cavity during peritoneal dialysis (PD). This study investigated AM behavior in PD patients, revealing its local activation.
Area of Science:
- Biochemistry
- Nephrology
- Cell Biology
Background:
- Adrenomedullin (AM) is a peptide hormone with vasodilative and cytoprotective functions.
- Glycine-mediated amidation converts AM to its mature, active form (mAM).
- AM is induced by high glucose, but its activation by amidation in peritoneal dialysis (PD) patients is poorly understood.
Purpose of the Study:
- To investigate the behavior and activation of Adrenomedullin (AM) in patients undergoing peritoneal dialysis (PD).
- To measure concentrations of AM, mature AM (mAM), and CA125 in PD effluent and plasma.
- To evaluate the mAM to AM ratio as a marker of amidation activity in the abdominal cavity.
Main Methods:
- Collected peritoneal dialysis effluent from 20 patients during the peritoneal equilibration test.
- Measured concentrations of AM, mAM, and CA125 in effluent and plasma.
- Examined AM expression in peritoneal mesothelial cells (PMCs) using indirect immunofluorescence.
Main Results:
- AM concentrations in effluent did not correlate with plasma AM but correlated with the dialysate-to-plasma creatinine ratio.
- In 7 out of 20 patients, effluent mAM concentrations and the mAM/AM ratio were higher than in plasma.
- AM, but not the mAM/AM ratio, correlated with CA125 in effluent; PMCs expressed AM in the cytoplasm.
Conclusions:
- Adrenomedullin (AM) is expressed by peritoneal mesothelial cells (PMCs) in patients undergoing PD.
- AM undergoes active amidation within the abdominal cavity during PD.
- The findings suggest local activation of AM in the peritoneal cavity of PD patients.
