J Appl Biomed 12:203-209, 2014 | DOI: 10.1016/j.jab.2014.07.001

Indoxyl sulfate stimulates oxidized LDL uptake through up-regulation of CD36 expression in THP-1 macrophages

Longxing Caoa, Qiang Fua, Bing Hui Wanga,b, Wen Jinc, Zhiliang Lia,*
a Cardiovascular Division, Zhujiang Hospital, Southern Medical University, Guangzhou, GD 510280, China
b Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic. 3004, Australia
c Cardiovascular Division, Guangdong No. 2 Provincial People's Hospital, Guangzhou, GD 510317, China

Indoxyl sulfate (IS), a uremic toxin, is considered as a risk factor for accelerated atherosclerosis in patients with chronic kidney disease. As uptake of oxidized low-density lipoprotein (Ox-LDL) in macrophages is a key event in the progression of atherosclerosis, the aim of this study was to determine direct effects of IS on uptake of Ox-LDL in macrophages. Flow cytometric analysis revealed that IS significantly stimulated Ox-LDL uptake by THP-1 macrophages in both dose- and time-dependent manners. A CD36 inhibitor, sulfosuccinimidyl oleate (SSO), and ERK1/2 inhibitors, PD98059 and U0126, could suppress the IS-stimulated Ox-LDL uptake. IS also stimulated CD36 expression, which was inhibited by PD98059 and U0126. Western blotting analysis showed that IS significantly activated ERK1/2 mitogen-activated protein kinase (MAPK) pathway by increasing its phosphorylation level. Further, CCK-8 assay showed that IS exerted its effects without affecting cell viability. In conclusion, IS stimulated Ox-LDL uptake through up-regulation of CD36 expression in THP-1 macrophages, partly via ERK1/2 MAPK pathway. This might be one of the mechanisms underlying the progression of atherosclerosis in patients with chronic kidney disease.

Keywords: Indoxyl sulfate; Oxidized LDL; Macrophages; ERK MAPK; Atherosclerosis

Received: April 16, 2014; Revised: June 23, 2014; Accepted: July 7, 2014; Published: November 1, 2014  Show citation

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Cao L, Fu Q, Hui Wang B, Jin W, Li Z. Indoxyl sulfate stimulates oxidized LDL uptake through up-regulation of CD36 expression in THP-1 macrophages. J Appl Biomed. 2014;12(4):203-209. doi: 10.1016/j.jab.2014.07.001.
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