title: ES cells overexpressing microRNA-1 attenuate apoptosis in the injured myocardium.
abstract: MicroRNAs (miRs) are small, single-stranded, noncoding RNA's involved in post-transcriptional negative gene regulation. Recent investigations have underscored the integral role of miRs in various biological processes including innate immunity, cell-cycle regulation, metabolism, differentiation, and cell death. In the present study, we overexpressed miR-1, a muscle-specific miR, in embryonic stem cells (miR-1-ES cells), transplanted them into the infarcted myocardium, and evaluated their impact on cardiac apoptosis and function. We provide evidence demonstrating reduced apoptosis following transplantation of miR-1-ES cells 4 weeks post-myocardial infarction as compared to respective controls assessed by TUNEL staining and a capsase-3 activity assay. Moreover, we show significant elevation in p-Akt levels and diminished PTEN levels in hearts transplanted with miR-1-ES cells as determined by enzyme-linked immunoassays. Finally, using echocardiography, we reveal mice receiving miR-1-ES cell transplantation post-myocardial infarction had significantly improved fractional shortening and ejection fraction compared with respective controls. Our data suggest transplanted miR-1-ES cells inhibit apoptosis, mediated through the PTEN/Akt pathway, leading to improved cardiac function in the infarcted myocardium.
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA.
authors.forename: Carley
authors.initials: C
authors.lastname: Glass
authors.forename: Dinender K
authors.initials: DK
authors.lastname: Singla
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004195:Disease Models, Animal; D004452:Echocardiography; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000637:transplantation*; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs; C517731:Mirn1 microRNA, mouse; D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase