Abstract
MicroRNAs (miRNAs) have emerged as a novel class of endogenous, small, noncoding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. Over 700 miRNAs have been identified and sequenced in humans, and the number of miRNA genes is estimated at more than 1000. Individual miRNA is functionally important as a transcription factor because it has the ability to regulate the expression of multiple genes through binding to its target with imperfect or perfect complement. In the heart, miRNAs have been involved in several clinical scenarios, such as ischemia/reperfusion (I/R) injury and heart failure suggesting that regulation of their function could be used as a novel cardioprotective strategy. In particular, miRNA-1, miRNA-21, miRNA-24, miRNA-29, miRNA-92a, miRNA-126, miRNA-133, miRNA-320, miRNA-199a, miRNA-208, and miRNA-195 have been shown to be regulated after I/R injury. Because tissue miRNAs can be released into circulating blood, they also offer exciting new opportunities for developing sensitive biomarkers, including miRNA-1, miRNA-126, miR-208, and miRNA-499, for acute myocardial infarction and other cardiac diseases.
Footnotes
This work was supported by the National Institutes of Health National Heart, Lung, and Blood Institute [Grants HL51045, HL59469, HL79424]; and an American Heart Association National Scientist Development Grant [Grant 10SDG3770011].
Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.
doi:10.1124/mol.111.073528.
-
ABBREVIATIONS:
- miRNA
- microRNA
- bp
- base pair(s)
- I/R
- ischemia/reperfusion
- MI
- myocardial infarction
- HSP
- heat shock protein
- PTEN
- phosphatase and tensin homolog deleted on chromosome ten
- LV
- left ventricle/left ventricular
- Bim
- Bcl-2 interacting mediator of cell death
- CUGBP2
- CUG triplet repeat-binding protein 2
- COX-2
- cyclooxygenase-2
- NS-398
- N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide
- DuP-697
- 5-bromo-2-(4-fluorophenyl)-3-(4-(methylsulfonyl)phenyl)-thiophene
- PC
- preconditioning
- HIF
- hypoxia-inducible factor
- PHD
- prolyl hydroxylase
- iNOS
- inducible nitric-oxide synthase
- AMI
- acute myocardial ischemia
- CK
- creatine kinase.
- Received May 10, 2011.
- Accepted July 7, 2011.
- Copyright © 2011 The American Society for Pharmacology and Experimental Therapeutics
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|