TY - JOUR
T1 - The glucose degradation product methylglyoxal induces immature angiogenesis in patients undergoing peritoneal dialysis
AU - Nakano, Toshiaki
AU - Kumiko, Torisu
AU - Mizumasa, Tohru
AU - Kuroki, Yusuke
AU - Tsuruya, Kazuhiko
AU - Kitazono, Takanari
N1 - Funding Information:
We thank Mariko Maura, Hideko Noguchi, Hiroshi Fujii, and Mikio Munakata for their excellent technical assistance. This work was supported by the 19th Baxter PD fund Award and partly by a JSPS KAKENHI Grant-in-Aid for Scientific Research C (No. 23590400 ). We thank Edanz Group ( www.edanzediting.com/ac ) for editing a draft of this manuscript.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/5/7
Y1 - 2020/5/7
N2 - The accumulation of glucose degradation products (GDPs) can lead to tissue damage in patients with diabetes and those undergoing long-term peritoneal dialysis (PD). Angiogenesis is occasionally observed in the peritoneal membrane of patients undergoing PD, where it is associated with failure of ultrafiltration. To investigate the mechanism underlying the influence of angiogenesis on fluid absorption, we evaluated the effects of accumulation of the glucose degradation product methylglyoxal (MGO) on angiogenesis in vitro, and analyzed the association with angiogenesis in the peritoneal membrane. To this end, we measured the levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)-BB in cultured endothelial and smooth muscle cells after administration of MGO. The expression of PDGF-BB mRNA and protein decreased significantly after exposure to MGO, while the expression of VEGF mRNA increased (both P < 0.01). The expression of PDGF-Rβ mRNA in cultured smooth muscle cells did not change after administration of MGO, although the expression of VEGF mRNA increased (P < 0.01). We also evaluated the associations between the number of capillary vessels, peritoneal function, and the degree of MGO deposition using peritoneum samples collected from patients undergoing PD. The number of immature capillary vessels was significantly associated with peritoneal dysfunction and the degree of MGO accumulation (both P < 0.01). In conclusion, MGO enhances the production of VEGF and suppresses the production of PDGF-BB, potentially leading to disturbance of angiogenesis in the peritoneal membrane. Accumulation of MGO in the peritoneum may cause immature angiogenesis and peritoneal dysfunction.
AB - The accumulation of glucose degradation products (GDPs) can lead to tissue damage in patients with diabetes and those undergoing long-term peritoneal dialysis (PD). Angiogenesis is occasionally observed in the peritoneal membrane of patients undergoing PD, where it is associated with failure of ultrafiltration. To investigate the mechanism underlying the influence of angiogenesis on fluid absorption, we evaluated the effects of accumulation of the glucose degradation product methylglyoxal (MGO) on angiogenesis in vitro, and analyzed the association with angiogenesis in the peritoneal membrane. To this end, we measured the levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)-BB in cultured endothelial and smooth muscle cells after administration of MGO. The expression of PDGF-BB mRNA and protein decreased significantly after exposure to MGO, while the expression of VEGF mRNA increased (both P < 0.01). The expression of PDGF-Rβ mRNA in cultured smooth muscle cells did not change after administration of MGO, although the expression of VEGF mRNA increased (P < 0.01). We also evaluated the associations between the number of capillary vessels, peritoneal function, and the degree of MGO deposition using peritoneum samples collected from patients undergoing PD. The number of immature capillary vessels was significantly associated with peritoneal dysfunction and the degree of MGO accumulation (both P < 0.01). In conclusion, MGO enhances the production of VEGF and suppresses the production of PDGF-BB, potentially leading to disturbance of angiogenesis in the peritoneal membrane. Accumulation of MGO in the peritoneum may cause immature angiogenesis and peritoneal dysfunction.
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U2 - 10.1016/j.bbrc.2020.02.048
DO - 10.1016/j.bbrc.2020.02.048
M3 - Article
C2 - 32147098
AN - SCOPUS:85080972727
SN - 0006-291X
VL - 525
SP - 767
EP - 772
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -
