PMID- 27060359 OWN - NLM STAT- MEDLINE DCOM- 20171127 LR - 20171201 IS - 1613-4133 (Electronic) IS - 1613-4125 (Linking) VI - 60 IP - 9 DP - 2016 Sep TI - Urolithin A attenuates ox-LDL-induced endothelial dysfunction partly by modulating microRNA-27 and ERK/PPAR-gamma pathway. PG - 1933-43 LID - 10.1002/mnfr.201500827 [doi] AB - 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 mug/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 alpha, interleukin 6, and endothelin 1, and increased PPAR-gamma (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-gamma decrease. Furthermore, UA significantly downregulated phosphorylated ERK1/2 (where ERK is extracellular signal-regulated kinase) while decreasing interleukin 6 level and elevating PPAR-gamma. CONCLUSIONS: UA could alleviate endothelial dysfunction induced by ox-LDL partially through modulating miR-27 expression and ERK/PPAR-gamma pathway. CI - (c) 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Han, Qi-An AU - Han QA AD - College of Food Science and Engineering, Northwest A&F University, Shaanxi, China. FAU - Yan, Chunhong AU - Yan C AD - School of Life Science and Technology, Xi'an Jiaotong University, Shaanxi, China. FAU - Wang, Lingfang AU - Wang L AD - College of Food Science and Engineering, Northwest A&F University, Shaanxi, China. FAU - Li, Guanghui AU - Li G AD - Food and Bioengineering College, Xuchang University, Xuchang, China. FAU - Xu, Yunfeng AU - Xu Y AD - College of Food Science and Engineering, Northwest A&F University, Shaanxi, China. FAU - Xia, Xiaodong AU - Xia X AD - College of Food Science and Engineering, Northwest A&F University, Shaanxi, China. foodscixiaodong@yahoo.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160531 PL - Germany TA - Mol Nutr Food Res JT - Molecular nutrition & food research JID - 101231818 RN - 0 (Coumarins) RN - 0 (Lipoproteins, LDL) RN - 0 (MIRN27 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (PPAR gamma) RN - 0 (Protective Agents) RN - 0 (oxidized low density lipoprotein) RN - 1143-70-0 (3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 1.14.13.39 (NOS3 protein, human) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) SB - IM MH - Cell Adhesion/drug effects MH - Cell Line MH - Coumarins/*pharmacology MH - Endothelium, Vascular/*drug effects/metabolism/physiopathology MH - Humans MH - L-Lactate Dehydrogenase/metabolism MH - Lipoproteins, LDL/*metabolism MH - MAP Kinase Signaling System/drug effects MH - MicroRNAs/*metabolism MH - Monocytes/drug effects MH - Nitric Oxide/metabolism MH - Nitric Oxide Synthase Type III/metabolism MH - PPAR gamma/genetics/*metabolism MH - Protective Agents/pharmacology OTO - NOTNLM OT - Atherosclerosis OT - ERK signal pathway OT - Endothelial dysfunction OT - MicroRNA-27 OT - Urolithin A EDAT- 2016/04/10 06:00 MHDA- 2017/11/29 06:00 CRDT- 2016/04/10 06:00 PHST- 2015/10/22 00:00 [received] PHST- 2016/03/18 00:00 [revised] PHST- 2016/03/28 00:00 [accepted] PHST- 2016/04/10 06:00 [entrez] PHST- 2016/04/10 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] AID - 10.1002/mnfr.201500827 [doi] PST - ppublish SO - Mol Nutr Food Res. 2016 Sep;60(9):1933-43. doi: 10.1002/mnfr.201500827. Epub 2016 May 31.