High density lipoprotein suppresses lipoprotein associated phospholipase A2 in human monocytes-derived macrophages through peroxisome proliferator-activated receptor-γ pathway.

Abstract

BACKGROUND:

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is mainly secreted by macrophages, serving as a specific marker of atherosclerotic plaque and exerting pro-atherogenic effects. It is known that high-density lipoprotein (HDL) plays an important role against atherosclerosis by inhibiting pro-inflammatory factors, however, the relationship between HDL and Lp-PLA2 remains elusive.

METHODS:

In this study, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and a platelet-activating factor (PAF) acetylhydrolase assay were performed to determine the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages upon HDL treatment of different concentrations and durations. To investigate the underlying mechanism of HDL-induced Lp-PLA2 action, pioglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ) ligand, was introduced to human monocyte-derived macrophages and mRNA and protein levels of Lp-PLA2, as well as its activity, were determined.

RESULTS:

Lp-PLA2 mRNA levels, protein expression and activity were significantly inhibited in response to HDL treatment in a dose and time dependent manner in human monocyte-derived macrophages. Pioglitazone treatment (1 - 10 ng/ml) upregulated the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages, while the effects were markedly reversed by HDL. In addition, pioglitazone resulted in a significant increase in PPARγ phosphorylation in human monocyte-derived macrophages, which could be inhibited by HDL.

CONCLUSION:

These findings indicate that HDL suppresses the expression and activity of Lp-PLA2 in human monocyte-derived macrophages, and the underlying mechanisms may be mediated through the PPARγ pathway.

• Authors: Guan-ping Han, Jing-yi Ren, Li Qin, Jun-xian Song, Lan Wang, Hong Chen
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 125 Issue 24 Pg. 4474-80 (Dec 2012) ISSN: 2542-5641 [Electronic] China
• PMID: 23253723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipoproteins, HDL
• PPAR gamma
• 1-Alkyl-2-acetylglycerophosphocholine Esterase

Topics

• 1-Alkyl-2-acetylglycerophosphocholine Esterase (genetics, metabolism)
• Cells, Cultured
• Humans
• Lipoproteins, HDL (pharmacology)
• Macrophages (drug effects, enzymology, metabolism)
• PPAR gamma (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects, genetics)