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Myeloperoxidase Mediates Postischemic Arrhythmogenic Ventricular Remodeling

M. Mollenhauer, K. Friedrichs, M. Lange, J. Gesenberg, L. Remane, C. Kerkenpaß, J. Krause, J. Schneider, T. Ravekes, M. Maass, M. Halbach, G. Peinkofer, T. Saric, D. Mehrkens, M. Adam, FG. Deuschl, D. Lau, B. Geertz, K. Manchanda, T. Eschenhagen,...

. 2017 ; 121 (1) : 56-70. [pub] 20170412

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc17030886

RATIONALE: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase, a heme enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. OBJECTIVE: To reveal the role of myeloperoxidase for the development of ventricular arrhythmias. METHODS AND RESULTS: In different murine models of myocardial ischemia, myeloperoxidase deficiency profoundly decreased vulnerability for ventricular tachycardia on programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry after isoproterenol injection. Experiments using CD11b/CD18 integrin-deficient (CD11b(-/-)) mice and intravenous myeloperoxidase infusion revealed that neutrophil infiltration is a prerequisite for myocardial myeloperoxidase accumulation. Ventricles from myeloperoxidase-deficient (Mpo(-/-)) mice showed less pronounced slowing and decreased heterogeneity of electric conduction in the peri-infarct zone than wild-type mice. Expression of the redox-sensitive gap junctional protein Cx43 (Connexin 43) was reduced in the peri-infarct area of wild-type compared with Mpo(-/-) mice. In isolated wild-type cardiomyocytes, Cx43 protein content decreased on myeloperoxidase/H2O2 incubation. Mapping of induced pluripotent stem cell-derived cardiomyocyte networks and in vivo investigations linked Cx43 breakdown to myeloperoxidase-dependent activation of matrix metalloproteinase 7. Moreover, Mpo(-/-) mice showed decreased ventricular postischemic fibrosis reflecting reduced accumulation of myofibroblasts. Ex vivo, myeloperoxidase was demonstrated to induce fibroblast-to-myofibroblast transdifferentiation by activation of p38 mitogen-activated protein kinases resulting in upregulated collagen generation. In support of our experimental findings, baseline myeloperoxidase plasma levels were independently associated with a history of ventricular arrhythmias, sudden cardiac death, or implantable cardioverter-defibrillator implantation in a cohort of 2622 stable patients with an ejection fraction >35% undergoing elective diagnostic cardiac evaluation. CONCLUSIONS: Myeloperoxidase emerges as a crucial mediator of postischemic myocardial remodeling and may evolve as a novel pharmacological target for secondary disease prevention after myocardial ischemia.

Citace poskytuje Crossref.org

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$a Mollenhauer, Martin $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
245    10
$a Myeloperoxidase Mediates Postischemic Arrhythmogenic Ventricular Remodeling / $c M. Mollenhauer, K. Friedrichs, M. Lange, J. Gesenberg, L. Remane, C. Kerkenpaß, J. Krause, J. Schneider, T. Ravekes, M. Maass, M. Halbach, G. Peinkofer, T. Saric, D. Mehrkens, M. Adam, FG. Deuschl, D. Lau, B. Geertz, K. Manchanda, T. Eschenhagen, L. Kubala, TK. Rudolph, Y. Wu, WHW. Tang, SL. Hazen, S. Baldus, A. Klinke, V. Rudolph,
520    9_
$a RATIONALE: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase, a heme enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. OBJECTIVE: To reveal the role of myeloperoxidase for the development of ventricular arrhythmias. METHODS AND RESULTS: In different murine models of myocardial ischemia, myeloperoxidase deficiency profoundly decreased vulnerability for ventricular tachycardia on programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry after isoproterenol injection. Experiments using CD11b/CD18 integrin-deficient (CD11b(-/-)) mice and intravenous myeloperoxidase infusion revealed that neutrophil infiltration is a prerequisite for myocardial myeloperoxidase accumulation. Ventricles from myeloperoxidase-deficient (Mpo(-/-)) mice showed less pronounced slowing and decreased heterogeneity of electric conduction in the peri-infarct zone than wild-type mice. Expression of the redox-sensitive gap junctional protein Cx43 (Connexin 43) was reduced in the peri-infarct area of wild-type compared with Mpo(-/-) mice. In isolated wild-type cardiomyocytes, Cx43 protein content decreased on myeloperoxidase/H2O2 incubation. Mapping of induced pluripotent stem cell-derived cardiomyocyte networks and in vivo investigations linked Cx43 breakdown to myeloperoxidase-dependent activation of matrix metalloproteinase 7. Moreover, Mpo(-/-) mice showed decreased ventricular postischemic fibrosis reflecting reduced accumulation of myofibroblasts. Ex vivo, myeloperoxidase was demonstrated to induce fibroblast-to-myofibroblast transdifferentiation by activation of p38 mitogen-activated protein kinases resulting in upregulated collagen generation. In support of our experimental findings, baseline myeloperoxidase plasma levels were independently associated with a history of ventricular arrhythmias, sudden cardiac death, or implantable cardioverter-defibrillator implantation in a cohort of 2622 stable patients with an ejection fraction >35% undergoing elective diagnostic cardiac evaluation. CONCLUSIONS: Myeloperoxidase emerges as a crucial mediator of postischemic myocardial remodeling and may evolve as a novel pharmacological target for secondary disease prevention after myocardial ischemia.
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$a Friedrichs, Kai $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Lange, Max $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Gesenberg, Jan $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
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$a Remane, Lisa $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
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$a Kerkenpaß, Christina $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
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$a Krause, Jenny $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Schneider, Johanna $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Ravekes, Thorben $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Maass, Martina $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Halbach, Marcel $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Peinkofer, Gabriel $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Saric, Tomo $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Mehrkens, Dennis $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Adam, Matti $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.). $7 gn_A_00001111
700    1_
$a Deuschl, Florian G $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Lau, Denise $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Geertz, Birgit $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Manchanda, Kashish $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Eschenhagen, Thomas $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Kubala, Lukas $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Rudolph, Tanja K $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Wu, Yuping $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Tang, W H Wilson $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Hazen, Stanley L $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Baldus, Stephan $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Klinke, Anna $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.).
700    1_
$a Rudolph, Volker $u From the Cardiology, Heart Center (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), Center for Molecular Medicine Cologne (M.M., K.F., M.L., J.G., L.R., C.K., J.S., T.R., M.M., M.H., G.P., D.M., M.A., K.M., T.K.R., S.B., A.K., V.R.), and Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty (T.S.), University of Cologne, Germany; University Heart Center Hamburg, Germany (J.K., D.L.); General and Interventional Cardiology (F.G.D.) and Experimental Pharmacology and Toxicology (B.G., T.E.), University Heart Center Hamburg, University Hospital Hamburg-Eppendorf (UKE), Germany; Institute of Biophysics, Czech Academy of Sciences, Brno (L.K.); International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic (L.K., A.K.); Mathematics, Cleveland State University, OH (Y.W.); and Cellular and Molecular Medicine and Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T., S.L.H.). volker.rudolph@uk-koeln.de.
773    0_
$w MED00001092 $t Circulation research $x 1524-4571 $g Roč. 121, č. 1 (2017), s. 56-70
856    41
$u https://pubmed.ncbi.nlm.nih.gov/28404615 $y Pubmed
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$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20171025 $b ABA008
991    __
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$a ok $b bmc $g 1254479 $s 991913
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$a 2017 $b 121 $c 1 $d 56-70 $e 20170412 $i 1524-4571 $m Circulation research $n Circ Res $x MED00001092
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