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MicroRNA-21 Mediates Isoflurane-induced Cardioprotection against Ischemia-Reperfusion Injury via Akt/Nitric Oxide Synthase/Mitochondrial Permeability Transition Pore Pathway.
Qiao, Shigang; Olson, Jessica M; Paterson, Mark; Yan, Yasheng; Zaja, Ivan; Liu, Yanan; Riess, Matthias L; Kersten, Judy R; Liang, Mingyu; Warltier, David C; Bosnjak, Zeljko J; Ge, Zhi-Dong.
Afiliação
  • Qiao S; Department of Anesthesiology (S.Q., J.M.O., M.P., Y.Y., I.Z., Y.L., J.R.K., D.C.W., Z.J.B., Z.D.G.), Department of Physiology (J.M.O., M.L., Z.J.B.), and Department of Pharmacology and Toxicology (J.R.K., D.C.W.), Medical College of Wisconsin, Milwaukee, Wisconsin, and Department of Anesthesiology (
  • Olson JM; Department of Anesthesiology (S.Q., J.M.O., M.P., Y.Y., I.Z., Y.L., J.R.K., D.C.W., Z.J.B., Z.D.G.), Department of Physiology (J.M.O., M.L., Z.J.B.), and Department of Pharmacology and Toxicology (J.R.K., D.C.W.), Medical College of Wisconsin, Milwaukee, Wisconsin, and Department of Anesthesiology (
  • Paterson M; Department of Anesthesiology (S.Q., J.M.O., M.P., Y.Y., I.Z., Y.L., J.R.K., D.C.W., Z.J.B., Z.D.G.), Department of Physiology (J.M.O., M.L., Z.J.B.), and Department of Pharmacology and Toxicology (J.R.K., D.C.W.), Medical College of Wisconsin, Milwaukee, Wisconsin, and Department of Anesthesiology (
  • Yan Y; Department of Anesthesiology (S.Q., J.M.O., M.P., Y.Y., I.Z., Y.L., J.R.K., D.C.W., Z.J.B., Z.D.G.), Department of Physiology (J.M.O., M.L., Z.J.B.), and Department of Pharmacology and Toxicology (J.R.K., D.C.W.), Medical College of Wisconsin, Milwaukee, Wisconsin, and Department of Anesthesiology (
  • Zaja I; Department of Anesthesiology (S.Q., J.M.O., M.P., Y.Y., I.Z., Y.L., J.R.K., D.C.W., Z.J.B., Z.D.G.), Department of Physiology (J.M.O., M.L., Z.J.B.), and Department of Pharmacology and Toxicology (J.R.K., D.C.W.), Medical College of Wisconsin, Milwaukee, Wisconsin, and Department of Anesthesiology (
  • Liu Y; Department of Anesthesiology (S.Q., J.M.O., M.P., Y.Y., I.Z., Y.L., J.R.K., D.C.W., Z.J.B., Z.D.G.), Department of Physiology (J.M.O., M.L., Z.J.B.), and Department of Pharmacology and Toxicology (J.R.K., D.C.W.), Medical College of Wisconsin, Milwaukee, Wisconsin, and Department of Anesthesiology (
  • Riess ML; Department of Anesthesiology (S.Q., J.M.O., M.P., Y.Y., I.Z., Y.L., J.R.K., D.C.W., Z.J.B., Z.D.G.), Department of Physiology (J.M.O., M.L., Z.J.B.), and Department of Pharmacology and Toxicology (J.R.K., D.C.W.), Medical College of Wisconsin, Milwaukee, Wisconsin, and Department of Anesthesiology (
  • Kersten JR; Department of Anesthesiology (S.Q., J.M.O., M.P., Y.Y., I.Z., Y.L., J.R.K., D.C.W., Z.J.B., Z.D.G.), Department of Physiology (J.M.O., M.L., Z.J.B.), and Department of Pharmacology and Toxicology (J.R.K., D.C.W.), Medical College of Wisconsin, Milwaukee, Wisconsin, and Department of Anesthesiology (
  • Liang M; Department of Anesthesiology (S.Q., J.M.O., M.P., Y.Y., I.Z., Y.L., J.R.K., D.C.W., Z.J.B., Z.D.G.), Department of Physiology (J.M.O., M.L., Z.J.B.), and Department of Pharmacology and Toxicology (J.R.K., D.C.W.), Medical College of Wisconsin, Milwaukee, Wisconsin, and Department of Anesthesiology (
  • Warltier DC; Department of Anesthesiology (S.Q., J.M.O., M.P., Y.Y., I.Z., Y.L., J.R.K., D.C.W., Z.J.B., Z.D.G.), Department of Physiology (J.M.O., M.L., Z.J.B.), and Department of Pharmacology and Toxicology (J.R.K., D.C.W.), Medical College of Wisconsin, Milwaukee, Wisconsin, and Department of Anesthesiology (
  • Bosnjak ZJ; Department of Anesthesiology (S.Q., J.M.O., M.P., Y.Y., I.Z., Y.L., J.R.K., D.C.W., Z.J.B., Z.D.G.), Department of Physiology (J.M.O., M.L., Z.J.B.), and Department of Pharmacology and Toxicology (J.R.K., D.C.W.), Medical College of Wisconsin, Milwaukee, Wisconsin, and Department of Anesthesiology (
  • Ge ZD; Department of Anesthesiology (S.Q., J.M.O., M.P., Y.Y., I.Z., Y.L., J.R.K., D.C.W., Z.J.B., Z.D.G.), Department of Physiology (J.M.O., M.L., Z.J.B.), and Department of Pharmacology and Toxicology (J.R.K., D.C.W.), Medical College of Wisconsin, Milwaukee, Wisconsin, and Department of Anesthesiology (
Anesthesiology ; 123(4): 786-798, 2015 Oct.
Article em En | MEDLINE | ID: mdl-26259139
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:

C57BL/6 and microRNA-21 knockout mice were echocardiographically examined. Mouse hearts underwent 30 min of ischemia followed by 2 h of reperfusion in vivo or ex vivo in the presence or absence of 1.0 minimum alveolar concentration of isoflurane administered before ischemia. Cardiac Akt, endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) proteins were determined by Western blot analysis. Opening of the mitochondrial permeability transition pore (mPTP) in cardiomyocytes was induced by photoexcitation-generated oxidative stress and detected by rapid dissipation of tetramethylrhodamine ethyl ester fluorescence using a confocal microscope.

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:

Isoflurane protects mouse hearts from ischemia-reperfusion injury by a microRNA-21-dependent mechanism. The Akt/NOS/mPTP pathway is involved in the microRNA-21-mediated protective effect of isoflurane.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão Miocárdica / Óxido Nítrico Sintase / Proteínas de Transporte da Membrana Mitocondrial / MicroRNAs / Proteínas Proto-Oncogênicas c-akt / Isoflurano Limite: Animals Idioma: En Revista: Anesthesiology Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão Miocárdica / Óxido Nítrico Sintase / Proteínas de Transporte da Membrana Mitocondrial / MicroRNAs / Proteínas Proto-Oncogênicas c-akt / Isoflurano Limite: Animals Idioma: En Revista: Anesthesiology Ano de publicação: 2015 Tipo de documento: Article