Lipoprotein-associated phospholipase A2: The story continues

doi:10.1002/med.21597

	Lipoprotein-associated phospholipase A2: The story continues
	Huang, Fubao 1,2; Wang, Kai 1; Shen, Jianhua 1
刊名	MEDICINAL RESEARCH REVIEWS
	2020
卷号	40 期号:1 页码:79-134
关键词	fragment-based lead discovery inflammation inhibitors lipoprotein-associated phospholipase A2 vascular diseases
ISSN号	0198-6325
DOI	10.1002/med.21597
通讯作者	Wang, Kai(kwang@simm.ac.cn) ; Shen, Jianhua(jhshen@simm.ac.cn)
英文摘要	Inflammation is thought to play an important role in the pathogenesis of vascular diseases. Lipoprotein-associated phospholipase A2 (Lp-PLA2) mediates vascular inflammation through the regulation of lipid metabolism in blood, thus, it has been extensively investigated to identify its role in vascular inflammation-related diseases, mainly atherosclerosis. Although darapladib, the most advanced Lp-PLA2 inhibitor, failed to meet the primary endpoints of two large phase III trials in atherosclerosis patients cotreated with standard medical care, the research on Lp-PLA2 has not been terminated. Novel pathogenic, epidemiologic, genetic, and crystallographic studies regarding Lp-PLA2 have been reported recently, while novel inhibitors were identified through a fragment-based lead discovery strategy. More strikingly, recent clinical and preclinical studies revealed that Lp-PLA2 inhibition showed promising therapeutic effects in diabetic macular edema and Alzheimer's disease. In this review, we not only summarized the knowledge of LpPLA2 established in the past decades but also emphasized new findings in recent years. We hope this review could be valuable for helping researchers acquire a much deeper insight into the nature of Lp-PLA2, identify more potent and selective Lp-PLA2 inhibitors, and discover the potential indications of Lp-PLA2 inhibitors.
资助项目	Shanghai Committee of Science and Technology, China[18431901000] ; National Natural Science Foundation of China[81673302] ; National Natural Science Foundation of China[81602963] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program', China[2018ZX09711002006-014]
WOS关键词	PLATELET-ACTIVATING-FACTOR ; CORONARY-HEART-DISEASE ; ACETYLHYDROLASE PAF-AH ; SINGLE-NUCLEOTIDE POLYMORPHISMS ; ZINC-DEPENDENT INHIBITORS ; PLA2G7 GENE POLYMORPHISMS ; ORALLY-ACTIVE INHIBITORS ; BLOOD-BRAIN-BARRIER ; ACID-LABILE FACTOR ; A(2) LP-PLA(2)
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	WILEY
WOS记录号	WOS:000534635500006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280025]
专题	中国科学院上海药物研究所
通讯作者	Wang, Kai; Shen, Jianhua
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Sch Pharm, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Huang, Fubao,Wang, Kai,Shen, Jianhua. Lipoprotein-associated phospholipase A2: The story continues[J]. MEDICINAL RESEARCH REVIEWS,2020,40(1):79-134.
APA	Huang, Fubao,Wang, Kai,&Shen, Jianhua.(2020).Lipoprotein-associated phospholipase A2: The story continues.MEDICINAL RESEARCH REVIEWS,40(1),79-134.
MLA	Huang, Fubao,et al."Lipoprotein-associated phospholipase A2: The story continues".MEDICINAL RESEARCH REVIEWS 40.1(2020):79-134.