title: A novel anti-inflammatory mechanism of high density lipoprotein through up-regulating annexin A1 in vascular endothelial cells.
abstract: High density lipoprotein (HDL) as well as annexin A1 have been reported to be associated with cardiovascular protection. However, the correlation between HDL and annexin A1 was still unknown. In this study, HDL increased endothelial annexin A1 and prevented the decrease of annexin A1 in TNF-α-activated endothelial cells in vitro and in vivo, and above effects were attenuated after knockdown of annexin A1. Annexin A1 modulation affected HDL-mediated inhibition of monocyte adhesion to TNF-α-activated endothelium (45.2±13.7% decrease for annexin A1 RNA interference; 78.7±16.3% decrease for anti-Annexin A1 antibody blocking; 11.2±6.9% increase for Ad-ANXA1 transfection). Additionally, HDL up-regulated annexin A1 through scavenger receptor class B type I, involving ERK, p38MAPK, Akt and PKC signaling pathways, and respective inhibitors of these pathways attenuated HDL-induced annexin A1 expression as well as impaired HDL-mediated inhibition of monocyte-endothelial cell adhesion. Apolipoprotein AI also increased annexin A1 and activated similar signaling pathways. Endothelial annexin A1 from apolipoprotein AI knockout mice was decreased in comparison to that from wild type mice. Finally, HDL-induced annexin A1 inhibited cell surface VCAM-1, ICAM-1 and E-selectin, and secretion of MCP-1, IL-8, VCAM-1 and E-selectin, thereby inhibiting monocyte adhesion.
authors.affiliation: Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Pan
authors.affiliation: Neuroscience Research Institute, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Key Laboratory for Neuroscience (Ministry of Education), Peking University Health Science Center, Beijing 100191, China; Key Laboratory for Neuroscience (National Health and Family Planning Commission), Peking University Health Science Center, Beijing 100191, China; Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Jinge
authors.initials: J
authors.lastname: Kong
authors.affiliation: Southern Medical University, Guangzhou 510515, China; The Military General Hospital of Beijing, Beijing 100700, China.
authors.forename: Jingru
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Hepatobiliary Surgery, West Campus, Beijing Chao-yang Hospital Affiliated to Capital Medical University, No. 5 Jingyuan Road, Shijingshan District, Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Kong
authors.affiliation: The Military General Hospital of Beijing, Beijing 100700, China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Hepatobiliary Surgery, West Campus, Beijing Chao-yang Hospital Affiliated to Capital Medical University, No. 5 Jingyuan Road, Shijingshan District, Beijing, China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Dong
authors.affiliation: Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ji
authors.affiliation: Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Pediatrics, Beijing Ren-he Hospital, Beijing 102600, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Kong
authors.affiliation: Ansary Stem Cell Institute, Weill Cornell Medical College, Cornell University, New York, NY 10027, USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Jin
authors.affiliation: Proteomics Laboratory, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Belinda
authors.initials: B
authors.lastname: Willard
authors.affiliation: Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Pennathur
authors.affiliation: Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing 100191, China. Electronic address: zhengl@bjmu.edu.cn.
authors.forename: Lemin
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000494:pharmacology; D015153:Blotting, Western; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D017305:Annexin A1; D016632:Apolipoprotein A-I; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; D008075:Lipoproteins, HDL; D014409:Tumor Necrosis Factor-alpha
keywords: Annexin A1; Endothelial cell; High density lipoprotein; Monocyte adhesion