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MicroRNA modulation of cardioprotective pathways
Author(s) -
Luther Kristin,
Mallick Faryal,
Jones W. K.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb615
Subject(s) - cardioprotection , microrna , ischemic preconditioning , gene , western blot , reperfusion injury , microbiology and biotechnology , myocardial infarction , signal transduction , biology , ischemia , pharmacology , bioinformatics , computational biology , medicine , cardiology , genetics
Every year, tens of thousands of Americans suffer a myocardial infarction. Cardioprotection (CP), the reduction of myocardial injury, involves the induction of pro‐survival processes and genes. Preconditioning of the myocardium can bring about CP through activation of an NF‐kB dependent gene program, in which research shows a key regulatory role for miRNA. Our data indicate the existence of an interconnected regulatory network of miRNAs and protective genes from multiple pathways, which are crucial to the adaptive stress responses of CP. The hypothesis of this study is that preconditioning causes a decrease in several regulatory miRNAs, facilitating an increase in protective protein expression. We preconditioned HL‐1 cardiomyocytes through oxygen and glucose deprivation, which significantly decreased cell death upon subsequent ischemia‐reperfusion injury. Levels of miRNAs and their predicted target genes were assayed by Realtime PCR and western blot. The results confirmed that the miRNAs decreased, while expression of the proteins increased. The data support that through their ability to target multiple genes, miRNAs act to coordinate multiple CP pathways. Insight into the role of miRNAs in CP will allow therapeutic modulation of miRNA levels using antagomirs, which represents an attractive clinical approach to reduce infarct size. This research was supported by NIH R01HL091478.