Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Clin Exp Nephrol. 2022 Dec;26(12):1160-1169. doi: 10.1007/s10157-022-02272-3. Epub 2022 Sep 7.
The accumulation of glucose degradation products (GDPs) during peritoneal dialysis (PD) can lead to immature angiogenesis in the peritoneum. However, the effect of GDPs on angiogenesis, at concentrations observed in dialysate effluent, has not been widely investigated. We do not know how the inflammation observed in PD-related peritonitis affects angiogenesis of the peritoneum.
Human umbilical vessel endothelial cells (HUVEC) and human umbilical aortic smooth muscle cells (HUASMC) were used to examine the response to the three main GDPs found in peritoneal dialysate (methylglyoxal (MGO), 3-deoxyglucosone (3-DG), and 5-hydroxymethylfurfural (5-HMF). Supernatant from lipopolysaccharide (LPS)-activated murine macrophage cell lines (RAW 264.7 cells) were used to stimulate angiogenesis in the peritoneum. Changes in the expression of vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor B (PDGFB) in HUVEC, and PDGF-receptor beta (PDGF-Rβ) in HUASMC, were examined by real-time PCR, Western blot, and ELISA.
In HUVECs, the expression of PDGFB mRNA and protein were decreased by exposure to MGO, 3-DG, and 5-HMF at concentrations observed in dialysate effluent. A subsequent decrease in secreted PDGF-BB was observed. In HUASMCs, MGO and 5-HMF increased the expression of VEGF-A mRNA and protein, while 5-HMF decreased the expression of PDGF-Rβ. VEGF-A is upregulated, and PDGF-Rβ is downregulated, by conditioned medium of LPS-stimulated macrophages in HUASMCs.
The GDPs of PD effluent cause an imbalance of angiogenic factors in endothelial cells and vascular smooth muscle cells that may lead to immature angiogenesis in the peritoneum.
在腹膜透析（PD）过程中葡萄糖降解产物（GDPs）的积累会导致腹膜内不成熟的血管生成。然而，在透析液流出物中观察到的 GDPs 浓度对血管生成的影响尚未得到广泛研究。我们不知道 PD 相关腹膜炎中观察到的炎症如何影响腹膜的血管生成。
用人脐血管内皮细胞（HUVEC）和人脐主动脉平滑肌细胞（HUASMC）来检测在腹膜透析液中发现的三种主要 GDPs（甲基乙二醛（MGO）、3-脱氧葡萄糖（3-DG）和 5-羟甲基糠醛（5-HMF）的反应。用脂多糖（LPS）激活的鼠巨噬细胞系（RAW 264.7 细胞）的上清液刺激腹膜中的血管生成。通过实时 PCR、Western blot 和 ELISA 检测 HUVEC 中血管内皮生长因子 A（VEGF-A）和血小板衍生生长因子 B（PDGFB）的表达变化，以及 HUASMC 中 PDGF 受体 β（PDGF-Rβ）的表达变化。
在 HUVEC 中，暴露于透析液流出物中观察到的浓度的 MGO、3-DG 和 5-HMF 会降低 PDGFB mRNA 和蛋白的表达，并观察到分泌的 PDGF-BB 减少。在 HUASMC 中，MGO 和 5-HMF 增加了 VEGF-A mRNA 和蛋白的表达，而 5-HMF 降低了 PDGF-Rβ 的表达。在 HUASMC 中，LPS 刺激的巨噬细胞的条件培养基上调了 VEGF-A，下调了 PDGF-Rβ。
PD 流出液中的 GDPs 导致内皮细胞和血管平滑肌细胞中血管生成因子失衡，可能导致腹膜内不成熟的血管生成。
