Institute of Nephrology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, NO. 321, Zhongshan Road, Nanjing, 210008, Jiangsu, China.
J Nephrol. 2019 Feb;32(1):101-110. doi: 10.1007/s40620-018-0486-2. Epub 2018 May 14.
Chronic inflammation plays an important role in the progression of vascular calcification (VC). This study was designed to explore the effects and underlying mechanisms of inflammation on VC in the radial arteries of patients with end-stage renal disease (ESRD) with arteriovenostomy.
Forty-eight ESRD patients were divided into control (n = 25) and inflammation groups (n = 23) according to plasma C-reactive protein (CRP) level. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used in this study. Alizarin Red S staining was used to examine calcium deposition. The expression of inflammation markers, bone structure-associated proteins and mammalian target of rapamycin complex1 (mTORC1) pathway-related proteins was assessed by immunohistochemical staining.
The expression of tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) was increased in the radial arteries of the inflammation group. Additionally, Alizarin Red S staining revealed a marked increase in calcium deposition in the inflammation group compared to controls. Further analysis by immunohistochemical staining demonstrated that the deposition was correlated with the increased expression of bone-associated proteins such as bone morphogenetic proteins-2 (BMP-2) and osteocalcin and collagen I, which suggested that inflammation induces osteogenic differentiation in vascular tissues and that osteogenic cells are the main cellular components involved in VC. Interestingly, there was a parallel increase in the expression of phosphorylated mTOR (p-mTOR) and pribosomal protein S6 kinase 1 (p-S6K1) in the inflammation group. Furthermore, mTORC1 pathway-related proteins were significantly associated with the enhanced expression of bone formation biomarkers.
Inflammation contributed to VC in the radial arteries of ESRD patients via the induction of osteogenic differentiation in vessel walls, which could be regulated by the activation of the mTORC1 pathway.
慢性炎症在血管钙化（VC）的进展中起着重要作用。本研究旨在探讨炎症对接受动静脉吻合术的终末期肾病（ESRD）患者桡动脉 VC 的影响及其潜在机制。
根据血浆 C 反应蛋白（CRP）水平，将 48 例 ESRD 患者分为对照组（n=25）和炎症组（n=23）。本研究使用了接受动静脉吻合术患者桡动脉的手术切除组织。茜素红 S 染色用于检查钙沉积。通过免疫组织化学染色评估炎症标志物、骨结构相关蛋白和雷帕霉素哺乳动物靶标复合物 1（mTORC1）途径相关蛋白的表达。
炎症组患者桡动脉中肿瘤坏死因子-α（TNF-α）和单核细胞趋化蛋白-1（MCP-1）的表达增加。此外，与对照组相比，炎症组的茜素红 S 染色显示钙沉积明显增加。进一步的免疫组织化学染色分析表明，沉积与骨相关蛋白如骨形态发生蛋白-2（BMP-2）和骨钙素以及 I 型胶原的表达增加有关，这表明炎症诱导血管组织中的成骨分化，而成骨细胞是 VC 中主要的细胞成分。有趣的是，炎症组中磷酸化 mTOR（p-mTOR）和核糖体蛋白 S6 激酶 1（p-S6K1）的表达也平行增加。此外，mTORC1 途径相关蛋白与增强的骨形成生物标志物表达显著相关。
炎症通过诱导血管壁中的成骨分化导致 ESRD 患者桡动脉中的 VC，这可以通过 mTORC1 途径的激活来调节。
