PMID- 26018800 OWN - NLM STAT- MEDLINE DCOM- 20160728 LR - 20150921 IS - 1613-4133 (Electronic) IS - 1613-4125 (Linking) VI - 59 IP - 9 DP - 2015 Sep TI - omega3-polyunsaturated fatty acids suppress lipoprotein-associated phospholipase A2 expression in macrophages and animal models. PG - 1771-9 LID - 10.1002/mnfr.201500022 [doi] AB - SCOPE: omega3-polyunsaturated fatty acids (omega3-PUFAs) have beneficial effects on cardiovascular function, and lipoprotein-associated phospholipase A2 (Lp-PLA2 ) is associated with the risk of cardiovascular disease. Here, we investigated the effects of omega3-PUFAs on Lp-PLA2 expression in vitro and in vivo and explored the mechanisms involved. METHODS AND RESULTS: Human monocyticcells (THP-1) were induced into macrophages in an in vitro model. omega3-PUFAs suppressed Lp-PLA2 expression; the suppression induced by docosahexaenoic acid (DHA) was related to reduced inflammation. Tumor necrosis factor-alpha (TNF-alpha) was employed to stimulate the phosphorylation of p38 mitogen-activated protein kinase (MAPK), nuclear factor-kappaB (NF-kappaB) p65 and Lp-PLA2 expression in macrophages. The stimulation was inhibited by DHA and the anti-inflammatory drug sodium salicylate. Moreover, the stimulation of Lp-PLA2 expression by TNF-alpha could be suppressed by NF-kappaB and MAPK pathway inhibitors. Then, chronic inflammation was induced in an in vivo mouse model, resulting in an increase in Lp-PLA2 expression in peripheral blood mononuclear cells (PBMCs) and arteries. This increase was suppressed by omega3-PUFAs. Inhibition of Lp-PLA2 transcription in PBMCs was also observed in omega3-PUFA-enriched swine. CONCLUSION: Our results demonstrate that the protective effects of omega3-PUFAs against cardiovascular events may be related to the suppression of Lp-PLA2 levels. CI - (c) 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Li, Zhuang AU - Li Z AD - Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, China. FAU - Ren, Wenzhi AU - Ren W AD - Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, China. FAU - Han, Xiaolei AU - Han X AD - Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, China. FAU - Liu, Xingxing AU - Liu X AD - Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, China. FAU - Wang, Gangqi AU - Wang G AD - Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, China. FAU - Zhang, Mingjun AU - Zhang M AD - Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, China. FAU - Pang, Daxin AU - Pang D AD - Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, China. FAU - Ouyang, Hongsheng AU - Ouyang H AD - Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, China. FAU - Tang, Xiaochun AU - Tang X AD - Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150618 PL - Germany TA - Mol Nutr Food Res JT - Molecular nutrition & food research JID - 101231818 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Fatty Acids, Omega-3) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - 25167-62-8 (Docosahexaenoic Acids) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.1.1.47 (1-Alkyl-2-acetylglycerophosphocholine Esterase) RN - EC 3.1.1.47 (PLA2G7 protein, human) SB - IM MH - 1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics/*metabolism MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Cardiovascular Diseases/prevention & control MH - Cell Line MH - Disease Models, Animal MH - Docosahexaenoic Acids/pharmacology MH - Down-Regulation MH - Fatty Acids, Omega-3/*pharmacology MH - *Gene Expression Regulation MH - Humans MH - Leukocytes, Mononuclear/drug effects/metabolism MH - Macrophages/*drug effects/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B/genetics/metabolism MH - Phosphorylation MH - Tumor Necrosis Factor-alpha/metabolism MH - p38 Mitogen-Activated Protein Kinases/genetics/metabolism OTO - NOTNLM OT - Cardiovascular disease OT - Inflammation OT - Lipoprotein associated phospholipase A2 OT - Signaling pathways OT - omega3-polyunsaturated fatty acids EDAT- 2015/05/29 06:00 MHDA- 2016/07/29 06:00 CRDT- 2015/05/29 06:00 PHST- 2015/01/09 00:00 [received] PHST- 2015/04/25 00:00 [revised] PHST- 2015/05/18 00:00 [accepted] PHST- 2015/05/29 06:00 [entrez] PHST- 2015/05/29 06:00 [pubmed] PHST- 2016/07/29 06:00 [medline] AID - 10.1002/mnfr.201500022 [doi] PST - ppublish SO - Mol Nutr Food Res. 2015 Sep;59(9):1771-9. doi: 10.1002/mnfr.201500022. Epub 2015 Jun 18.