Faculty of Science, Beirut Arab University, Debbieh, Lebanon.
Laboratiore de Biotechnologie, Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon.
Inflammation. 2019 Dec;42(6):2003-2010. doi: 10.1007/s10753-019-01061-7.
Inflammation and cardiovascular disease (CVD) are common in end-stage renal disease (ESRD) patients whose vascular endothelium is in direct contact with the uremic toxins found in the blood. These toxins are believed to affect vascular injury and repair process, which is impaired in ESRD patients. The exact mechanisms behind these interactions are not clear. So, we wanted to investigate what happens at the molecular level of endothelial cells when exposed to uremic serum from ESRD patients with diabetes and/or hypertension and its effect on the expression of molecules associated with vascular injury and repair. Cultured human endothelial cells (ECV304) were incubated in the presence of normal or uremic sera from ESRD patients with diabetes and/or hypertension. The expressions of monocyte chemoattractant protein 1 (MCP-1), vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SDF-1) were investigated in endothelial cells (ECV304) by real-time PCR and ELISA. The expression of MCP-1, VEGF, and SDF-1 was elevated in endothelial cells upon exposure to uremic sera from ESRD patients with diabetes and/or hypertension when compared with cells treated with healthy serum. MCP-1 expression in endothelial cells treated with uremic serum from ESRD patients with hypertension only was significantly increased compared with its expression in other cohorts. Exposure of endothelial cells to uremic serum causes endothelial injury and inflammation characterized by an increase in MCP-1 expression. This injury activates the initiation of vascular repair process in these cells by increasing the expression of VEGF and SDF-1. These molecules can be important biomarkers of chronic kidney disease-associated CVD.
在终末期肾病(ESRD)患者中,炎症和心血管疾病(CVD)很常见,这些患者的血管内皮与血液中的尿毒症毒素直接接触。这些毒素被认为会影响血管损伤和修复过程,而 ESRD 患者的这种过程受损。这些相互作用的确切机制尚不清楚。因此,我们想研究当暴露于患有糖尿病和/或高血压的 ESRD 患者的尿毒症血清时,内皮细胞在分子水平上会发生什么,以及它对与血管损伤和修复相关的分子表达的影响。将培养的人内皮细胞(ECV304)在存在正常或尿毒症血清的情况下孵育来自患有糖尿病和/或高血压的 ESRD 患者。通过实时 PCR 和 ELISA 研究内皮细胞(ECV304)中单核细胞趋化蛋白 1(MCP-1)、血管内皮生长因子(VEGF)和基质细胞衍生因子 1(SDF-1)的表达。与用健康血清处理的细胞相比,暴露于患有糖尿病和/或高血压的 ESRD 患者的尿毒症血清会导致内皮细胞中 MCP-1、VEGF 和 SDF-1 的表达升高。与其他队列相比,仅用高血压 ESRD 患者的尿毒症血清处理的内皮细胞中 MCP-1 的表达显著增加。内皮细胞暴露于尿毒症血清会导致内皮损伤和炎症,其特征是 MCP-1 表达增加。这种损伤通过增加 VEGF 和 SDF-1 的表达来激活这些细胞中血管修复过程的启动。这些分子可能是慢性肾脏病相关 CVD 的重要生物标志物。