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血浆糖萼模式:慢性肾脏病内皮损伤的一面镜子

Plasma glycocalyx pattern: a mirror of endothelial damage in chronic kidney disease.

作者信息

Valera Gemma, Figuer Andrea, Caro Jara, Yuste Claudia, Morales Enrique, Ceprián Noemí, Bodega Guillermo, Ramírez Rafael, Alique Matilde, Carracedo Julia

机构信息

Departamento de Genética, Fisiología y Microbiología, Facultad de Ciencias Biológicas, Universidad Complutense de Madrid/Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain.

Departamento de Biología de Sistemas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.

出版信息

Clin Kidney J. 2023 Mar 20;16(8):1278-1287. doi: 10.1093/ckj/sfad051. eCollection 2023 Aug.

Abstract

BACKGROUND

Endothelial damage and cardiovascular disease complicate chronic kidney disease (CKD). The increased atherogenicity observed in patients with CKD can be linked to microinflammation and endothelial damage. Circulating endothelial glycocalyx degradation products, such as perlecan and decorin, tend to be elevated in CKD. We aimed to explore the association between the plasma perlecan and decorin levels and this pro-inflammatory and atherogenic state by studying monocyte subpopulations and intracellular adhesion molecule (ICAM)-1 expression in patients with CKD.

METHODS

We studied 17 healthy controls, 23 patients with advanced CKD, 25 patients on haemodialysis, 23 patients on peritoneal dialysis and 20 patients who underwent kidney transplantation. Perlecan and decorin levels were evaluated using enzyme-linked immunosorbent assays, and the monocyte phenotype was analysed using direct immunofluorescence and flow cytometry.

RESULTS

The plasma perlecan levels were higher in patients with CKD than in the healthy controls. These levels were associated with a higher prevalence of ICAM-1+ monocytes. Conversely, patients with advanced CKD (pre-dialysis) had higher plasma decorin levels, which were associated with a reduced ICAM-1 expression per monocyte.

CONCLUSIONS

Elevated perlecan levels in CKD may be associated with a higher prevalence of ICAM-1+ monocytes and a pro-inflammatory phenotype. Elevated decorin levels may act as a negative regulator of ICAM-1 expression in monocytes. Therefore, perlecan and decorin may be related to inflammation and monocyte activation in CKD and may act as potential markers of endothelial damage.

摘要

背景

内皮损伤和心血管疾病使慢性肾脏病(CKD)病情复杂化。CKD患者中观察到的动脉粥样硬化性增加可能与微炎症和内皮损伤有关。循环中的内皮糖萼降解产物,如基底膜聚糖和核心蛋白聚糖,在CKD患者中往往会升高。我们旨在通过研究CKD患者的单核细胞亚群和细胞间黏附分子(ICAM)-1表达,探讨血浆基底膜聚糖和核心蛋白聚糖水平与这种促炎和动脉粥样硬化状态之间的关联。

方法

我们研究了17名健康对照者、23名晚期CKD患者、25名血液透析患者、23名腹膜透析患者和20名接受肾移植的患者。使用酶联免疫吸附测定法评估基底膜聚糖和核心蛋白聚糖水平,并使用直接免疫荧光和流式细胞术分析单核细胞表型。

结果

CKD患者的血浆基底膜聚糖水平高于健康对照者。这些水平与ICAM-1+单核细胞的较高患病率相关。相反,晚期CKD(透析前)患者的血浆核心蛋白聚糖水平较高,这与每个单核细胞的ICAM-1表达降低有关。

结论

CKD中基底膜聚糖水平升高可能与ICAM-1+单核细胞的较高患病率和促炎表型相关。核心蛋白聚糖水平升高可能作为单核细胞中ICAM-1表达的负调节因子。因此,基底膜聚糖和核心蛋白聚糖可能与CKD中的炎症和单核细胞活化有关,并可能作为内皮损伤的潜在标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8553/10387401/7e5ab2b5e350/sfad051fig1g.jpg

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