title: Urolithin A attenuates ox-LDL-induced endothelial dysfunction partly by modulating microRNA-27 and ERK/PPAR-γ pathway.
abstract: 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.
  
  
  
  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.
  
  
  
  UA could alleviate endothelial dysfunction induced by ox-LDL partially through modulating miR-27 expression and ERK/PPAR-γ pathway.
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, Shaanxi, China.
authors.forename: Qi-An
authors.initials: QA
authors.lastname: Han
authors.affiliation: School of Life Science and Technology, Xi'an Jiaotong University, Shaanxi, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Yan
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, Shaanxi, China.
authors.forename: Lingfang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Food and Bioengineering College, Xuchang University, Xuchang, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Li
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, Shaanxi, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, Shaanxi, China. foodscixiaodong@yahoo.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xia
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D003374:Coumarins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D035683:MicroRNAs / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology
chemical_list: D003374:Coumarins; D008077:Lipoproteins, LDL; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D047495:PPAR gamma; D020011:Protective Agents; C099252:oxidized low density lipoprotein; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Atherosclerosis; ERK signal pathway; Endothelial dysfunction; MicroRNA-27; Urolithin A