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ω3-polyunsaturated fatty acids suppress lipoprotein-associated phospholipase A2 expression in macrophages and animal models.

AbstractSCOPE:
ω3-polyunsaturated fatty acids (ω3-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 ω3-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. ω3-PUFAs suppressed Lp-PLA2 expression; the suppression induced by docosahexaenoic acid (DHA) was related to reduced inflammation. Tumor necrosis factor-α (TNF-α) was employed to stimulate the phosphorylation of p38 mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB) 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-α could be suppressed by NF-κB 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 ω3-PUFAs. Inhibition of Lp-PLA2 transcription in PBMCs was also observed in ω3-PUFA-enriched swine.
CONCLUSION:
Our results demonstrate that the protective effects of ω3-PUFAs against cardiovascular events may be related to the suppression of Lp-PLA2 levels.
AuthorsZhuang Li, Wenzhi Ren, Xiaolei Han, Xingxing Liu, Gangqi Wang, Mingjun Zhang, Daxin Pang, Hongsheng Ouyang, Xiaochun Tang
JournalMolecular nutrition & food research (Mol Nutr Food Res) Vol. 59 Issue 9 Pg. 1771-9 (Sep 2015) ISSN: 1613-4133 [Electronic] Germany
PMID26018800 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Chemical References
  • Anti-Inflammatory Agents
  • Fatty Acids, Omega-3
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Docosahexaenoic Acids
  • p38 Mitogen-Activated Protein Kinases
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • PLA2G7 protein, human
Topics
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase (genetics, metabolism)
  • Animals
  • Anti-Inflammatory Agents (pharmacology)
  • Cardiovascular Diseases (prevention & control)
  • Cell Line
  • Disease Models, Animal
  • Docosahexaenoic Acids (pharmacology)
  • Down-Regulation
  • Fatty Acids, Omega-3 (pharmacology)
  • Gene Expression Regulation
  • Humans
  • Leukocytes, Mononuclear (drug effects, metabolism)
  • Macrophages (drug effects, metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B (genetics, metabolism)
  • Phosphorylation
  • Tumor Necrosis Factor-alpha (metabolism)
  • p38 Mitogen-Activated Protein Kinases (genetics, metabolism)

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