Nitro-oleic acid downregulates lipoprotein-associated phospholipase A2 expression via the p42/p44 MAPK and NF kappa B pathways

作者：Wang, Gangqi; Ji, Yuan; Li, Zhuang; Han, Xiaolei; Guo, Nannan; Song, Qi; Quan, Longquan; Wang, Tiedong; Han, Wenyu; Pang, Daxin; Ouyang, Hongsheng; Tang, Xiaochun^*

来源：Scientific Reports, 2014, 4(1): 4905.

DOI：10.1038/srep04905

• LOW-DENSITY-LIPOPROTEIN
• NITRATED FATTY-ACIDS
• NITROLINOLEIC ACID
• OXIDE
• ATHEROSCLEROSIS
• TRANSDUCTION
• A(2)
• INFLAMMATION
• MACROPHAGES
• METABOLISM

Nitro-oleic acid (OA-NO2), acting as anti-inflammatory signaling mediators, are involved in multiple signaling pathways. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is well known as a cardiovascular risk biomarker. Our results showed that OA-NO2 downregulated the expression of Lp-PLA2 in a time-and dose-dependent manner, whereas native OA had no such effect. Furthermore, OA-NO2 could repress Lp-PLA2 expression in the peripheral blood mononuclear cells of apo CIII-transgenic (apo CIII TG) pigs, which exhibited higher Lp-PLA2 expression and activity than did wild-type (WT) pigs. OA-NO2 inhibited Lp-PLA2 expression in macrophages, independent of nitric oxide formation and PPAR gamma-activation. However, OA-NO2 downregulates Lp-PLA2 by inhibiting the p42/p44 mitogen-activated protein kinase (MAPK) and the nuclear factor kappa B (NF kappa B) pathways. When used to mediate anti-inflammatory signaling, the regulation of inflammatory cytokines and SOD by OA-NO2 might be associated with the reduction of Lp-PLA2. These results suggested that OA-NO2 might exert a vascular-protective effect partially via Lp-PLA2 inhibition.

• 出版日期2014-5-9
• 单位吉林大学