Effect of serum from patients with chronic renal insufficiency and indoxyl sulfate on lipid accumulation in macrophages in vitro
10.3969/j.issn.1673-4254.2015.05.03
- VernacularTitle:慢性肾功能不全患者血清及硫酸吲哚酚对巨噬细胞脂质聚集的影响
- Author:
Yan SHEN
1
;
Pei WANG
;
Juan ZHOU
;
Zuyi YUAN
;
Aiping YIN
;
Lijun WANG
Author Information
1. 西安交通大学医学院第一附属医院 肾病中心肾内科
- Keywords:
chronic renal insufficiency;
atherosclerosis;
indoxyl sulfate;
macrophages;
CD36;
foam cells
- From:
Journal of Southern Medical University
2015;(5):631-638
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the pathologies of aortic root atherosclerotic lesion in uremic apoE-/-mice and explore the effect of serum from patients with chronic renal insufficiency (CRI) and the uremic toxin, indoxyl sulfate (IS), on the expression of cholesterol transporting receptors and lipid accumulation in macrophages in vitro. Methods The uremic apoE-/-mouse model was established by surgical operation. Frozen sections of the aortic root were collected from uremic apoE-/-mice, sham-operated apoE-/- mice and C57BL/6J mice and stained with oil red O to calculate the relative area of atherosclerotic plaque. Murine macrophage RAW264.7 cell line was treated for 12 h with different concentrations of IS or serum samples from CRI patients and healthy individuals, and the mRNA expressions of cholesterol transporting receptors (SR-A1, CD36, ABCA1, ABCG1 and SR-B1) were detected. After treatment for 24 h, the cells were induced into foam cells to determine lipid contents using oil red O staining. Results The relative area of the atherosclerotic plaques in the aortic root increased significantly in uremic apoE-/- mice compared with that in sham-operated apoE-/- mice. CRI serum (5%) and IS (250 μmol/L) obviously increased the mRNA expression of CD36 and lipid accumulation in the macrophages, but did not affect the mRNA expression of other cholesterol transporting receptors. Conclusion CRI can accelerate the progression of atherosclerosis through the mechanism that IS in CRI serum promotes lipid accumulation in macrophages by enhancing the mRNA expression of CD36, which contributes to the formation of foam cells.