OxLDL stimulates lipoprotein-associated phospholipase A(2) expression in THP-1 monocytes via PI3K and p38 MAPK pathways

doi:10.1093/cvr/cvp367

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	OxLDL stimulates lipoprotein-associated phospholipase A(2) expression in THP-1 monocytes via PI3K and p38 MAPK pathways
	Wang, Wen-Yi 1,2; Li, Jie 2; Yang, Ding 2; Xu, Wei 1,2; Zha, Ruo-peng 1,2; Wang, Yi-ping2
刊名	CARDIOVASCULAR RESEARCH
	2010-03-01
卷号	85 期号:4 页码:845-852
关键词	Atherosclerosis lp-PLA2 oxLDL p38 PI3K
ISSN号	0008-6363
DOI	10.1093/cvr/cvp367
文献子类	Article
英文摘要	Lipoprotein-associated phospholipase A(2) (lp-PLA(2)) has been detected in human and rabbit atherosclerotic lesions, where it co-localizes with its substrate, oxidized LDL (oxLDL). Here, we investigated whether oxLDL may exert a regulatory effect on lp-PLA(2) expression. Using human monocytic THP-1 cells as a model system, we found that oxLDL up-regulated the expression of lp-PLA(2) while another substrate of the enzyme, platelet activating factor, had no such effect. The up-regulatory effect of oxLDL could be conferred by its oxidized phospholipids (oxPCs, the exact substrates of lp-PLA(2)), but not their hydrolyzed products, lysophosphatidylcholines (lysoPCs). OxLDL induced the activation of p38 mitogen-activating protein kinase (MAPK) through phosphatidylinositol 3-kinase (PI3K). Inhibition of either PI3K or p38 MAPK completely blocked oxLDL-induced lp-PLA(2) expression. In addition, inhibition of lp-PLA(2) activity in the conditioned medium significantly decreased lipid accumulation in macrophages as detected by oil red staining. The present study shows that oxLDL, and more specifically its unhydrolyzed oxidized phospholipids, can up-regulate lp-PLA(2) expression in monocytes through the PI3K and p38 MAPK pathway. In turn, lp-PLA(2) promotes lipoprotein uptake in macrophages. Our results uncover a new link between oxLDL and lp-PLA(2), and may provide insight into this interaction in the context of atherosclerosis.
资助项目	National Basic Research Program of China[2009CB930300]
WOS关键词	ACTIVATING-FACTOR-ACETYLHYDROLASE ; LOW-DENSITY-LIPOPROTEIN ; CORONARY-HEART-DISEASE ; PROTEIN-KINASE CASCADES ; OXIDIZED PHOSPHOLIPIDS ; ATHEROSCLEROTIC PLAQUE ; OXIDATION-PRODUCTS ; ARTERY-DISEASE ; RISK-FACTORS ; INFLAMMATION
WOS研究方向	Cardiovascular System & Cardiology
语种	英语
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000274487900024
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278959]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Wang, Yi-ping
作者单位	1.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Wang, Wen-Yi,Li, Jie,Yang, Ding,et al. OxLDL stimulates lipoprotein-associated phospholipase A(2) expression in THP-1 monocytes via PI3K and p38 MAPK pathways[J]. CARDIOVASCULAR RESEARCH,2010,85(4):845-852.
APA	Wang, Wen-Yi,Li, Jie,Yang, Ding,Xu, Wei,Zha, Ruo-peng,&Wang, Yi-ping.(2010).OxLDL stimulates lipoprotein-associated phospholipase A(2) expression in THP-1 monocytes via PI3K and p38 MAPK pathways.CARDIOVASCULAR RESEARCH,85(4),845-852.
MLA	Wang, Wen-Yi,et al."OxLDL stimulates lipoprotein-associated phospholipase A(2) expression in THP-1 monocytes via PI3K and p38 MAPK pathways".CARDIOVASCULAR RESEARCH 85.4(2010):845-852.