Urolithin A attenuates ox-LDL-induced endothelial dysfunction partly by modulating microRNA-27 and ERK/PPAR-γ pathway
- PMID: 27060359
- DOI: 10.1002/mnfr.201500827
Urolithin A attenuates ox-LDL-induced endothelial dysfunction partly by modulating microRNA-27 and ERK/PPAR-γ pathway
Abstract
Scope: Endothelial dysfunction and inflammation are both common events occurring during the development of atherosclerosis. Previous studies have shown that urolithins, the intestinal microflora metabolites of ellagitannin, exhibit anti-inflammation and antioxidative properties. This study aims to investigate the protective effect of urolithin A (UA) on ox-LDL-induced (where ox-LDL is oxidized low-density lipoprotein) endothelial dysfunction and possible modes of action.
Methods and results: Human artery endothelial cells were incubated with 50 μg/mL ox-LDL and various concentrations of UA for 24 h. UA improved the productions of nitric oxide and endothelial nitric oxide synthase in a dose-dependent manner. UA markedly reduced the expressions of ICAM-1 (intercellular adhesion molecule 1) and MCP-1 (monocyte chemotactic protein 1) and further attenuated THP-1 (human acute monocytic leukemia cell line) cell adhesion. In addition, UA suppressed expressions of tumor necrosis factor α, interleukin 6, and endothelin 1, and increased PPAR-γ (peroxisome proliferators activated receptor gamma) mRNA expression. Moreover, UA decreased miR-27 expression, and overexpression of miR-27 by adding pre-miR-27 abolished the ability of UA to improve ox-LDL-induced PPAR-γ decrease. Furthermore, UA significantly downregulated phosphorylated ERK1/2 (where ERK is extracellular signal-regulated kinase) while decreasing interleukin 6 level and elevating PPAR-γ.
Conclusions: UA could alleviate endothelial dysfunction induced by ox-LDL partially through modulating miR-27 expression and ERK/PPAR-γ pathway.
Keywords: Atherosclerosis; ERK signal pathway; Endothelial dysfunction; MicroRNA-27; Urolithin A.
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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