Annexin A5 inhibits atherogenic and pro-inflammatory effects of lysophosphatidylcholine

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• 作者：Helena Domeij ; Xiang Hua ; Jun Su ; Alex ; ra B盲cklund ; Zhongqun Yan ; Anna G. Frosteg氓rd ; Jesper Z. Haeggstr枚m ; Tomas Mod茅er ; Johan Frosteg氓rd
• 关键词：Atherosclerosis ; Inflammation ; Lysophosphatidylcholine ; Phospholipids ; Leukotrienes
• 刊名：Prostaglandins and Other Lipid Mediators
• 出版年：October, 2013
• 年：2013
• 卷：106
• 期：Complete
• 页码：72-78
• 全文大小：1363 K

文摘

Objective

Atherosclerosis is an inflammatory condition, and rupture of atherosclerotic plaques is a major cause of cardiovascular disease (CVD). Lysophosphatidylcholine (LPC) is generated in low-density lipoprotein (LDL) during oxidation and/or enzymatic modification and has been implicated in atherosclerosis. Annexin A5 (ANXA5) is an antithrombotic and atheroprotective plasma protein. Here, we demonstrate novel pro-inflammatory and atherogenic properties of LPC, and inhibitory effects of ANXA5.

Methods

Endothelial cells and macrophages (differentiated from, THP-1 a monocytic cell line) were co-cultured. Expression of MMP-9 and OxLDL uptake by macrophages were studied by flow cytometry. The effect of LPC on leukotriene B4 (LTB4) synthesis in macrophages was studied by enzyme immunoassay (EIA). Chemotactic properties of LPC were investigated using a mouse intra-peritoneal recruitment model.

Results

Co-culture of macrophages and endothelial cells enhanced MMP-9 expression in both cell types. This effect was increased by LPC and diminished by ANXA5. Likewise, LPC induced LTB4 production by macrophages, whereas native LDL or phosphatidylcholine (PTC) had no effect. ANXA5 inhibited uptake of OxLDL in macrophages. LPC induced cell infiltration in vivo, as determined by increased cell count in mouse peritoneal exudates, and this effect was inhibited by ANXA5.

Conclusions

ANXA5 could potentially play an important protective role in both atherogenesis and atherosclerotic plaque rupture by reducing pro-inflammatory effects of OxLDL and LPC as well as inhibiting OxLDL binding and uptake by macrophages. The possibility that ANXA5 could be developed into a novel therapy against CVD deserves further study.