title: MicroRNA expression signature and the role of microRNA-21 in the early phase of acute myocardial infarction.
abstract: Several recent reports have suggested that microRNAs (miRNAs) might play critical roles in acute myocardial infarction (AMI). However, the miRNA expression signature in the early phase of AMI has not been identified. In this study, the miRNA expression signature was investigated in rat hearts 6 h after AMI. Compared with the expression signature in the noninfarcted areas, 38 miRNAs were differentially expressed in infarcted areas and 33 miRNAs were aberrantly expressed in the border areas. Remarkably, miR-21 expression was significantly down-regulated in infarcted areas, but was up-regulated in border areas. The down-regulation of miR-21 in the infarcted areas was inhibited by ischemic preconditioning, a known cardiac protective method. Overexpression of miR-21 via adenovirus expressing miR-21 (Ad-miR-21) decreased myocardial infarct size by 29% at 24 h and decreased the dimension of left ventricles at 2 weeks after AMI. Using both gain-of-function and loss-of-function approaches in cultured cardiac myocytes, we identified that miR-21 had a protective effect on ischemia-induced cell apoptosis that was associated with its target gene programmed cell death 4 and activator protein 1 pathway. The protective effect of miR-21 against ischemia-induced cardiac myocyte damage was further confirmed in vivo by decreased cell apoptosis in the border and infarcted areas of the infarcted rat hearts after treatment with Ad-miR-21. The results suggest that miRNAs such as miR-21 may play critical roles in the early phase of AMI.
authors.affiliation: Department of Anesthesiology, RNA and Cardiovascular Research Laboratory, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07101, USA.
authors.forename: Shimin
authors.initials: S
authors.lastname: Dong
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Cheng
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Li
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Liu
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Krall
authors.forename: Ellise S
authors.initials: ES
authors.lastname: Delphin
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D035683:MicroRNAs
references.citation: Circ Res. 2007 Jun 8;100(11):1579-88
references.pmid: 17478730
references.citation: Nat Genet. 2005 Jul;37(7):766-70
references.pmid: 15965474
references.citation: Cell. 1993 Dec 3;75(5):855-62
references.pmid: 8252622
references.citation: Dev Cell. 2008 Aug;15(2):261-71
references.pmid: 18694565
references.citation: Genomics Proteomics Bioinformatics. 2005 May;3(2):62-72
references.pmid: 16393143
references.citation: Cell. 2003 Jun 13;113(6):673-6
references.pmid: 12809598
references.citation: Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2308-17
references.pmid: 16815986
references.citation: Science. 2005 Dec 16;310(5755):1817-21
references.pmid: 16308420
references.citation: Med Clin North Am. 2007 Jul;91(4):553-72; ix
references.pmid: 17640536
references.citation: J Card Surg. 2006 Nov-Dec;21(6):559-64
references.pmid: 17073953
references.citation: Nature. 2007 Jul 5;448(7149):83-6
references.pmid: 17589500
references.citation: EMBO J. 2007 Feb 7;26(3):775-83
references.pmid: 17255951
references.citation: J Mol Cell Cardiol. 2009 Jul;47(1):5-14
references.pmid: 19336275
references.citation: Nat Med. 2007 Apr;13(4):486-91
references.pmid: 17401374
references.citation: Physiol Genomics. 2007 Nov 14;31(3):367-73
references.pmid: 17712037
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5251-6
references.pmid: 9560262
references.citation: FEBS Lett. 2008 Dec 24;582(30):4137-42
references.pmid: 19041309
references.citation: Nat Rev Mol Cell Biol. 2005 May;6(5):376-85
references.pmid: 15852042
references.citation: Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2533-40
references.pmid: 16766632
references.citation: Science. 2001 Oct 26;294(5543):853-8
references.pmid: 11679670
references.citation: Basic Res Cardiol. 2004 Jul;99(4):264-71
references.pmid: 15221344
references.citation: Cell. 1993 Dec 3;75(5):843-54
references.pmid: 8252621
references.citation: Cell. 2005 Jan 14;120(1):15-20
references.pmid: 15652477
references.citation: Oncogene. 2001 Apr 30;20(19):2390-400
references.pmid: 11402335
references.citation: Gene Ther. 2007 Sep;14(18):1353-61
references.pmid: 17611588
references.citation: J Endocrinol. 2007 Nov;195(2):255-63
references.pmid: 17951536
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13027-32
references.pmid: 18723672
references.citation: Curr Opin Genet Dev. 2005 Apr;15(2):200-5
references.pmid: 15797203
references.citation: Cell. 2005 Jan 14;120(1):21-4
references.pmid: 15652478
references.citation: Science. 1986 Jan 31;231(4737):470-5
references.pmid: 3941911