The inhibition of lipoprotein-associated phospholipase A2 exerts beneficial effects against atherosclerosis in LDLR-deficient mice

doi:10.1038/aps.2011.127

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	The inhibition of lipoprotein-associated phospholipase A2 exerts beneficial effects against atherosclerosis in LDLR-deficient mice
	Hu, Miao-miao 1; Zhang, Jie 1; Wang, Wen-yi 1; Wu, Wen-yu 1; Ma, Yan-ling 1; Chen, Wei-hai 2,3; Wang, Yi-ping1
刊名	ACTA PHARMACOLOGICA SINICA
	2011-10
卷号	32 期号:10 页码:1253-1258
关键词	atherosclerosis lp-PLA2 darapladib LDLR-deficient mice inflammation high-sensitivity C-reactive protein interleukin-6 monocyte chemotactic protein-1 vascular cell adhesion molecule-1
ISSN号	1671-4083
DOI	10.1038/aps.2011.127
文献子类	Article
英文摘要	Aim: To investigate the effects of darapladib, a specific inhibitor of lipoprotein-associated phospholipase A2 (lp-PLA2), on inflammation and atherosclerotic formation in the low density lipoprotein receptor (LDLR)-deficient mice. Methods: Six-week-old LDLR-deficient mice were fed an atherogenic high-fat diet for 17 weeks and then randomly divided into two groups. One group was administered darapladib (50 mg.kg(-1).d(-1); po) for 6 weeks. The other group was administered saline as a control. Serum lipid levels were measured using the corresponding kits, and three inflammatory markers - interleukin-6 (IL-6), C reactive protein (hs-CRP), and platelet activating factor (PAF) - were determined using ELISA. Atherosclerotic plaque areas were stained with Sudan IV, and inflammatory gene expression at the lesions was evaluated using quantitative real-time PCR. Results: The body weight and serum lipid level between the two groups were similar at the end of the dietary period. The serum lp-PLA2 activity, hs-CRP and IL-6 levels, however, were significantly reduced in the darpladib group. The inhibition of lp-PLA2 did not alter the serum PAF level. Furthermore, the plaque area, from the aortic arch to the abdominal aorta, was significantly reduced in the darpladib group. Additionally, the expression of inflammatory genes monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) was significantly reduced at the lesions in the darapladib group. Conclusion: Inhibition of lp-PLA2 by darapladib decreases the inflammatory burden and atherosclerotic plaque formation in LDLR-deficient mice, which may be a new strategy for the treatment of atherosclerosis.
资助项目	Shanghai Committee of Science and Technology, China[11ZR1444800] ; National Basic Research Program of China[2009CB930300]
WOS关键词	PLATELET-ACTIVATING-FACTOR ; CORONARY-HEART-DISEASE ; LOW-DENSITY-LIPOPROTEIN ; C-REACTIVE PROTEIN ; MIDDLE-AGED MEN ; FACTOR-ACETYLHYDROLASE ; OXIDIZED PHOSPHOLIPIDS ; CARDIOVASCULAR EVENTS ; ARTERY-DISEASE ; RISK-FACTORS
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:4335575
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000295921300010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278382]
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, Shanghai Inst Mat Med, State Key Lab Drug Res, Dept Pharmacol 1, Shanghai 201203, Peoples R China; 2.Southwest Univ, Minist Educ, Key Lab Cognit & Personal SWU, Chongqing 400715, Peoples R China; 3.Southwest Univ, Sch Psychol, Chongqing 400715, Peoples R China
推荐引用方式 GB/T 7714	Hu, Miao-miao,Zhang, Jie,Wang, Wen-yi,et al. The inhibition of lipoprotein-associated phospholipase A2 exerts beneficial effects against atherosclerosis in LDLR-deficient mice[J]. ACTA PHARMACOLOGICA SINICA,2011,32(10):1253-1258.
APA	Hu, Miao-miao.,Zhang, Jie.,Wang, Wen-yi.,Wu, Wen-yu.,Ma, Yan-ling.,...&Wang, Yi-ping.(2011).The inhibition of lipoprotein-associated phospholipase A2 exerts beneficial effects against atherosclerosis in LDLR-deficient mice.ACTA PHARMACOLOGICA SINICA,32(10),1253-1258.
MLA	Hu, Miao-miao,et al."The inhibition of lipoprotein-associated phospholipase A2 exerts beneficial effects against atherosclerosis in LDLR-deficient mice".ACTA PHARMACOLOGICA SINICA 32.10(2011):1253-1258.