MicroRNA-21 Mediates Isoflurane-induced Cardioprotection against Ischemia–Reperfusion Injury via Akt/Nitric Oxide Synthase/Mitochondrial Permeability Transition Pore Pathway

DOI PDF Web Site 被引用文献2件
  • Shigang Qiao
    From the 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, Tennessee Valley Healthcare System Veterans Affairs Medical Center and Vanderbilt University, Nashville, Tennessee (M.L.R.).
  • Jessica M. Olson
    From the 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, Tennessee Valley Healthcare System Veterans Affairs Medical Center and Vanderbilt University, Nashville, Tennessee (M.L.R.).
  • Mark Paterson
    From the 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, Tennessee Valley Healthcare System Veterans Affairs Medical Center and Vanderbilt University, Nashville, Tennessee (M.L.R.).
  • Yasheng Yan
    From the 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, Tennessee Valley Healthcare System Veterans Affairs Medical Center and Vanderbilt University, Nashville, Tennessee (M.L.R.).
  • Ivan Zaja
    From the 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, Tennessee Valley Healthcare System Veterans Affairs Medical Center and Vanderbilt University, Nashville, Tennessee (M.L.R.).
  • Yanan Liu
    From the 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, Tennessee Valley Healthcare System Veterans Affairs Medical Center and Vanderbilt University, Nashville, Tennessee (M.L.R.).
  • Matthias L. Riess
    From the 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, Tennessee Valley Healthcare System Veterans Affairs Medical Center and Vanderbilt University, Nashville, Tennessee (M.L.R.).
  • Judy R. Kersten
    From the 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, Tennessee Valley Healthcare System Veterans Affairs Medical Center and Vanderbilt University, Nashville, Tennessee (M.L.R.).
  • Mingyu Liang
    From the 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, Tennessee Valley Healthcare System Veterans Affairs Medical Center and Vanderbilt University, Nashville, Tennessee (M.L.R.).
  • David C. Warltier
    From the 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, Tennessee Valley Healthcare System Veterans Affairs Medical Center and Vanderbilt University, Nashville, Tennessee (M.L.R.).
  • Zeljko J. Bosnjak
    From the 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, Tennessee Valley Healthcare System Veterans Affairs Medical Center and Vanderbilt University, Nashville, Tennessee (M.L.R.).
  • Zhi-Dong Ge
    From the 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, Tennessee Valley Healthcare System Veterans Affairs Medical Center and Vanderbilt University, Nashville, Tennessee (M.L.R.).

書誌事項

公開日
2015-10
DOI
  • 10.1097/aln.0000000000000807
公開者
Ovid Technologies (Wolters Kluwer Health)

この論文をさがす

説明

<jats:title>AbstractAbstract</jats:title><jats:p>Isoflurane protects mouse hearts from myocardial ischemia/reperfusion injury by a microRNA-21-dependent mechanism. The results of this article open a new area of investigation into epigenetic mechanisms of volatile anesthetic-induced cardiac protection.</jats:p><jats:sec><jats:title>Background:</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>C57BL/6 and microRNA-21 knockout mice were echocardiographically examined. Mouse hearts underwent 30 min of ischemia followed by 2 h of reperfusion i<jats:italic toggle="yes">n vivo</jats:italic>or<jats:italic toggle="yes">ex vivo</jats:italic>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.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>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% (<jats:italic toggle="yes">P</jats:italic>< 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p>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.</jats:p></jats:sec>

収録刊行物

  • Anesthesiology

    Anesthesiology 123 (4), 786-798, 2015-10

    Ovid Technologies (Wolters Kluwer Health)

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