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Up-regulation of microRNA-21 mediates isoflurane-induced protection of cardiomyocytes. Anesthesiology 2015 Apr;122(4):795-805

Date

12/24/2014

Pubmed ID

25536091

Pubmed Central ID

PMC4366274

DOI

10.1097/ALN.0000000000000567

Scopus ID

2-s2.0-84937250884   32 Citations

Abstract

BACKGROUND: Anesthetic cardioprotection reduces myocardial infarct size after ischemia-reperfusion injury. Currently, the role of microRNA in this process remains unknown. MicroRNAs are short, noncoding nucleotide sequences that negatively regulate gene expression through degradation or suppression of messenger RNA. In this study, the authors uncovered the functional role of microRNA-21 (miR-21) up-regulation after anesthetic exposure.

METHODS: MicroRNA and messenger RNA expression changes were analyzed by quantitative real-time polymerase chain reaction in cardiomyocytes after exposure to isoflurane. Lactate dehydrogenase release assay and propidium iodide staining were conducted after inhibition of miR-21. miR-21 target expression was analyzed by Western blot. The functional role of miR-21 was confirmed in vivo in both wild-type and miR-21 knockout mice.

RESULTS: Isoflurane induces an acute up-regulation of miR-21 in both in vivo and in vitro rat models (n = 6, 247.8 ± 27.5% and 258.5 ± 9.0%), which mediates protection to cardiomyocytes through down-regulation of programmed cell death protein 4 messenger RNA (n = 3, 82.0 ± 4.9% of control group). This protective effect was confirmed by knockdown of miR-21 and programmed cell death protein 4 in vitro. In addition, the protective effect of isoflurane was abolished in miR-21 knockout mice in vivo, with no significant decrease in infarct size compared with nonexposed controls (n = 8, 62.3 ± 4.6% and 56.2 ± 3.2%).

CONCLUSIONS: The authors demonstrate for the first time that isoflurane mediates protection of cardiomyocytes against oxidative stress via an miR-21/programmed cell death protein 4 pathway. These results reveal a novel mechanism by which the damage done by ischemia/reperfusion injury may be decreased.

Author List

Olson JM, Yan Y, Bai X, Ge ZD, Liang M, Kriegel AJ, Twaroski DM, Bosnjak ZJ

Authors

Xiaowen Bai PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Zeljko J. Bosnjak PhD Professor in the Medicine department at Medical College of Wisconsin
Alison J. Kriegel PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Mingyu Liang PhD Center Director, Professor in the Physiology department at Medical College of Wisconsin
Jessica Olson PhD Director, Assistant Professor in the Institute for Health and Equity department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Anesthetics, Inhalation
Animals
Animals, Newborn
Cardiotonic Agents
Cells, Cultured
Female
Isoflurane
Male
Mice
Mice, Knockout
MicroRNAs
Myocytes, Cardiac
Pregnancy
Random Allocation
Rats
Rats, Sprague-Dawley
Rats, Wistar
Up-Regulation