title: An agomir of miR-144-3p accelerates plaque formation through impairing reverse cholesterol transport and promoting pro-inflammatory cytokine production.
abstract: OBJECTIVE
  ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins, which then form nascent HDL, a key step in the mechanism of reverse cholesterol transport (RCT). While a series of microRNAs (miRNAs) have been identified as potent post-transcriptional regulators of lipid metabolism, their effects on ABCA1 function and associated mechanisms remain unclear.
  
  
  RESULTS
  ABCA1 was identified as a potential target of miR-144-3p, based on the results of bioinformatic analysis and the luciferase reporter assay, and downregulated after transfection of cells with miR-144-3p mimics, as observed with real-time PCR and western blot. Moreover, miR-144-3p mimics (agomir) enhanced the expression of inflammatory factors, including IL-1β, IL-6 and TNF-α, in vivo and in vitro, inhibited cholesterol efflux in THP-1 macrophage-derived foam cells, decreased HDL-C circulation and impaired RCT in vivo, resulting in accelerated pathological progression of atherosclerosis in apoE-/- mice. Clinical studies additionally revealed a positive correlation of circulating miR-144-3p with serum CK, CK-MB, LDH and AST in subjects with AMI.
  
  
  CONCLUSIONS
  Our findings clearly indicate that miR-144-3p is essential for the regulation of cholesterol homeostasis and inflammatory reactions, supporting its utility as a potential therapeutic target of atherosclerosis and a promising diagnostic biomarker of AMI.
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Hu
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Ya-Rong
authors.initials: YR
authors.lastname: Hu
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Zhao
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Shao-Guo
authors.initials: SG
authors.lastname: Wu
authors.affiliation: Department of Vascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Lu
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Qiu
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Sha
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yan-Chao
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Ji-Juan
authors.initials: JJ
authors.lastname: Gao
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000328:Adult; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D001692:Biological Transport; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000819:agonists* / Q000097:blood; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000235:genetics / Q000473:pathology*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D001057:Apolipoproteins E; D016207:Cytokines; D018836:Inflammation Mediators; D008074:Lipoproteins; C554293:MIRN144 microRNA, human; C551064:MIRN144 microRNA, mouse; D035683:MicroRNAs; D002784:Cholesterol
references.citation: Atherosclerosis. 2009 Jan;202(1):2-10
references.pmid: 18951547
references.citation: J Immunol Methods. 1984 Apr 13;69(1):71-7
references.pmid: 6715889
references.citation: Circulation. 2007 Apr 3;115(13):e356-75
references.pmid: 17384331
references.citation: JAMA. 2002 May 15;287(19):2570-81
references.pmid: 12020339
references.citation: Dis Markers. 2013;35(5):561-6
references.pmid: 24249943
references.citation: Lipids Health Dis. 2011 Oct 10;10:175
references.pmid: 21985435
references.citation: Biomarkers. 2013 Nov;18(7):547-58
references.pmid: 24025051
references.citation: J Biol Chem. 2011 Apr 22;286(16):13834-45
references.pmid: 21339300
references.citation: J Clin Invest. 2005 Oct;115(10):2870-4
references.pmid: 16200214
references.citation: Circulation. 2002 Mar 5;105(9):1135-43
references.pmid: 11877368
references.citation: Clin Biochem. 1995 Feb;28(1):1-29
references.pmid: 7720223
references.citation: Circulation. 2002 Nov 19;106(21):2700-6
references.pmid: 12438296
references.citation: Atherosclerosis. 2009 Jun;204(2):e35-43
references.pmid: 19070858
references.citation: Lab Invest. 2002 Mar;82(3):273-83
references.pmid: 11896206
references.citation: Clin Biochem. 2009 Sep;42(13-14):1444-51
references.pmid: 19523464
references.citation: Circulation. 2009 Mar 3;119(8):1135-45
references.pmid: 19221221
references.citation: Atheroscler Suppl. 2011 Nov;12(3):267-70
references.pmid: 22152280
references.citation: Onkologie. 1987 Aug;10(4):254-8
references.pmid: 2823200
references.citation: Biochim Biophys Acta. 2012 Mar;1821(3):522-9
references.pmid: 21920460
references.citation: JAMA. 2001 Nov 7;286(17):2107-13
references.pmid: 11694151
references.citation: J Lipid Res. 2001 Jul;42(7):1007-17
references.pmid: 11441126
references.citation: J Biol Chem. 1997 May 23;272(21):13597-607
references.pmid: 9153208
references.citation: J Clin Invest. 2002 Oct;110(7):905-11
references.pmid: 12370266
references.citation: Cell. 1998 Apr 17;93(2):241-52
references.pmid: 9568716
references.citation: Heart. 2010 Jul;96(13):1001-10
references.pmid: 20584855
references.citation: J Biol Chem. 2003 Aug 22;278(34):31610-20
references.pmid: 12775725
references.citation: J Lipid Res. 2001 Aug;42(8):1173-9
references.pmid: 11483617
references.citation: Arterioscler Thromb Vasc Biol. 2000 May;20(5):1262-75
references.pmid: 10807742
references.citation: Science. 1996 May 3;272(5262):685-8
references.pmid: 8614828
references.citation: J Biol Chem. 2000 Nov 3;275(44):34508-11
references.pmid: 10918070
references.citation: Science. 2010 Jun 18;328(5985):1570-3
references.pmid: 20466885
references.citation: Arterioscler Thromb Vasc Biol. 2009 Feb;29(2):261-7
references.pmid: 19008529
references.citation: J Intern Med. 2015 Feb;277(2):260-271
references.pmid: 24345063
references.citation: Nat Genet. 1999 Aug;22(4):336-45
references.pmid: 10431236
references.citation: PLoS One. 2012;7(12):e50926
references.pmid: 23236408
references.citation: Physiol Rev. 2003 Oct;83(4):1069-112
references.pmid: 14506301
references.citation: Curr Opin Lipidol. 2012 Jun;23(3):220-225
references.pmid: 22488426
references.citation: Br J Pharmacol. 2012 Nov;167(6):1177-94
references.pmid: 22725625
references.citation: Circ Cardiovasc Genet. 2014 Apr;7(2):189-98
references.pmid: 24627568
references.citation: J Hepatol. 2002 Apr;36(4):459-65
references.pmid: 11943415
references.citation: Int J Clin Exp Med. 2014 Jan 15;7(1):136-41
references.pmid: 24482699
references.citation: Arterioscler Thromb Vasc Biol. 2012 Dec;32(12):2813-20
references.pmid: 23152494
references.citation: Arterioscler Thromb Vasc Biol. 2003 May 1;23(5):720-7
references.pmid: 12615680
references.citation: Curr Atheroscler Rep. 2011 Apr;13(2):107-14
references.pmid: 21380938
references.citation: Science. 2010 Jun 18;328(5985):1566-9
references.pmid: 20466882
references.citation: Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1178-84
references.pmid: 12738681
references.citation: N Engl J Med. 2000 Sep 7;343(10):732-4
references.pmid: 10974140
references.citation: Arterioscler Thromb Vasc Biol. 1996 Jan;16(1):4-11
references.pmid: 8548424