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Overexpression of microRNA-1 impairs cardiac contractile function by damaging sarcomere assembly.
MedLine Citation:
PMID:  22719074     Owner:  NLM     Status:  Publisher    
AIM: The purpose of the present study was to evaluate the effects of overexpression of microRNA-1 (miR-1) on cardiac contractile function and the potential molecular mechanisms.Methods and ResultsTransgenic (Tg) mice (C57BL/6) for cardiac-specific overexpression of miR-1 driven by the α-myosin heavy chain (α-MHC) promoter were generated and identified by real-time reverse-transcription polymerase chain reaction with left ventricular samples. We found an age-dependent decrease in heart function in Tg mice by pressure-volume loop analysis. Histological analysis and electron microscopy displayed short sarcomeres with loss of the clear zone and H-zone as well as myofibril fragmentation and deliquescence in Tg mice. Further studies demonstrated miR-1 post-transcriptionally down-regulated the expression of calmodulin (CaM) and cardiac myosin light chain kinase (cMLCK) proteins by targeting the 3'UTRs of MYLK3, CALM1 and CALM2 genes, leading to decreased phosphorylations of myosin light chain 2v (MLC2v) and cardiac myosin binding protein-C (cMyBP-C). Knockdown of miR-1 by locked nucleic acid-modified anti-miR-1 antisense (LNA-antimiR-1) mitigated the adverse changes of cardiac function associated with overexpression of miR-1. CONCLUSIONS: MiR-1 induces adverse structural remodeling to impair cardiac contractile function. Targeting cMLCK and CaM likely underlies the detrimental effects of miR-1 on structural components of muscles related to the contractile machinery. Our study provides the first evidence for miRNA in causing adverse structural remodeling of the heart.
Jing Ai; Rong Zhang; Xu Gao; Hui-Fang Niu; Ning Wang; Yi Xu; Yue Li; Ning Ma; Li-Hua Sun; Zhen-Wei Pan; Wei-Min Li; Bao-Feng Yang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-18
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Pharmacology Harbin Medical University, No.157 Baojian Road, Nangang District, Harbin, 150081, China.
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