Urolithin A attenuates ox‐LDL‐induced endothelial dysfunction partly by modulating microRNA‐27 and ERK/PPAR‐γ pathway

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.