Abstract | BACKGROUND: The role of microRNA-21 in isoflurane-induced cardioprotection is unknown. The authors addressed this issue by using microRNA-21 knockout mice and explored the underlying mechanisms. METHODS: RESULTS: Genetic disruption of miR-21 gene did not alter phenotype of the left ventricle, baseline cardiac function, area at risk, and the ratios of phosphorylated-Akt/Akt, phosphorylated-eNOS/eNOS, and phosphorylated-nNOS/nNOS. Isoflurane decreased infarct size from 54 ± 10% in control to 36 ± 10% (P < 0.05, n = 8 mice per group), improved cardiac function after reperfusion, and increased the ratios of phosphorylated-Akt/AKT, phosphorylated-eNOS/eNOS, and phosphorylated-nNOS/nNOS in C57BL/6 mice subjected to ischemia-reperfusion injury. These beneficial effects of isoflurane were lost in microRNA-21 knockout mice. There were no significant differences in time of the mPTP opening induced by photoexcitation-generated oxidative stress in cardiomyocytes isolated between C57BL/6 and microRNA-21 knockout mice. Isoflurane significantly delayed mPTP opening in cardiomyocytes from C57BL/6 but not from microRNA-21 knockout mice. CONCLUSIONS:
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Authors | Shigang Qiao, Jessica M Olson, Mark Paterson, Yasheng Yan, Ivan Zaja, Yanan Liu, Matthias L Riess, Judy R Kersten, Mingyu Liang, David C Warltier, Zeljko J Bosnjak, Zhi-Dong Ge |
Journal | Anesthesiology
(Anesthesiology)
Vol. 123
Issue 4
Pg. 786-798
(Oct 2015)
ISSN: 1528-1175 [Electronic] United States |
PMID | 26259139
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Cardiotonic Agents
- MIRN21 microRNA, mouse
- MicroRNAs
- Mitochondrial Membrane Transport Proteins
- Mitochondrial Permeability Transition Pore
- Isoflurane
- Nitric Oxide Synthase
- Proto-Oncogene Proteins c-akt
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Topics |
- Animals
- Cardiotonic Agents
(administration & dosage)
- Cells, Cultured
- Isoflurane
(administration & dosage)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- MicroRNAs
(physiology)
- Mitochondrial Membrane Transport Proteins
(metabolism)
- Mitochondrial Permeability Transition Pore
- Myocardial Reperfusion Injury
(metabolism, prevention & control)
- Myocytes, Cardiac
(drug effects, metabolism)
- Nitric Oxide Synthase
(metabolism)
- Organ Culture Techniques
- Proto-Oncogene Proteins c-akt
(metabolism)
- Signal Transduction
(drug effects, physiology)
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