Phosphatase-1 inhibitor-1 in physiological and pathological β-adrenoceptor signalling.
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I-1 was found to be down-regulated and hypo-phosphorylated in human and experimental heart failure but hyperactive in human atrial fibrillation, implicating I-1 in the pathogenesis of heart failure and arrhythmias.Abstract:
Control of protein phosphorylation-dephosphorylation events occurs through regulation of protein kinases and phosphatases. Phosphatase type 1 (PP-1) provides the main activity of serine/threonine protein phosphatases in the heart. Inhibitor-1 (I-1) was the first endogenous molecule found to inhibit PP-1 specifically. Notably, I-1 is activated by cAMP-dependent protein kinase A (PKA), and the subsequent prevention of target dephosphorylation by PP-1 provides distal amplification of β-adrenoceptor (β-AR) signalling. I-1 was found to be down-regulated and hypo-phosphorylated in human and experimental heart failure but hyperactive in human atrial fibrillation, implicating I-1 in the pathogenesis of heart failure and arrhythmias. Consequently, the therapeutic potential of I-1 in heart failure and arrhythmias has recently been addressed by the generation and analysis of several I-1 genetic mouse models. This review summarizes and discusses these data, highlights partially controversial issues on whether I-1 should be therapeutically reinforced or inhibited and suggests future directions to better understand the functional role of I-1 in physiological and pathological β-AR signalling.read more
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References
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Journal ArticleDOI
Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)
Åke Hjalmarson,Sidney Goldstein,Björn Fagerberg,Hans Wedel,Finn Waagstein,John Kjekshus,John Wikstrand,G. Westergren,M. Thimell,D. El Allaf,Jiri Vitovec,J. Aldershvile,M. Halinen,Rainer Dietz,K. L. Neuhaus,András Jánosi,Gudmundur Thorgeirsson,P. Dunselman,Lars Gullestad,J. Kuch,Johan Herlitz,Peter Rickenbacher,Stephen G. Ball,Stephen S. Gottlieb,Prakash Deedwania,G. Vandenhoven,I. Nováková,S. Danker,M. Lundström,W. Meyer-Sabellek,I. Balla,M. Sveinsdottir,B. Dorhout,A. Hildebrandt,I. Szczurko,C. Larsson,E. Bucher,E. Scott,D. Dwyer,D. G. Julian,David L. DeMets,K. Chatterjee,J. Feyzi,S. Lehto,P. Karpati,W. Motz,O. Samuelsson,J. W. Viersma,B. Andersson,C. Berthe,J. M. Boutefeu,G. Boxho,P. Decroly,J. P. Derbaudrenghien,J. Pirlet,Philip D. Henry,G. Heyndrickx,L. Missault,M. Nannan,P. Timmermans,J. L. Vachiery,W. Van Mieghem,J. L. Vandenbossche,K. Dvorák,M. Herold,Jaromír Hradec,A. Kána,P. Petr,J. Rybka,J. Smíd,P. Svítil,J. Toman,E. Agner,O. Amtorp,K. Egstrup,P. Eliasen,C. O. Gotzsche,P. Hildebrandt,A. Johannesen,P. Kaiser-Nielsen,H. Nielsen,P. E. Nielsen,F. Pedersen,J. Rokkedal Nielsen,K. Skagen,T. Honkanen,E. Hussi,J. Juvonen,H. Jääskeläinen,J. Rinne,T. Salonen,D. Andresen,H. Berwing,Bethge,Beythien,Bischoff,Bundschu,Daniel,Darius,Delius,Drude,Dingerkus,Dück,Eichler,Fach,A. Förster,Girth,Goss,Hahn,Hambrecht,G. F. Hauf,Heinemann,Hepp,Janka,Klocke,Konz,B. Krosse,Kühlkamp,Lewek,B. Lüderitz,Löbe,Maier,Melchior,Müller,Mäurer,Nast,Neuhaus,Obst,Odemar,K. E. von Olshausen,Pomykaj,K. J.G. Schmailzl,Schrader,Schröder,P. L. Schwimmbeck,M. Sigmund,Simon,Strasser,Thilo,Vöhringer,H. Völler,Weibrodt,Wirtz,István Czuriga,M. Hetey,A. Katona,M. Lengyel,A. Nyárádi,A. Rednik,K. Sándori,P. Szabó,J. Tarján,J. Tenczer,S. Timar,P. Vályi,G. Veress,K. Zámolyi,B. Oze,Ge Thorgeirsson,Gu Thorgeirsson,P. J.L.M. Bernink,A. C. Bredero,R. Breedveld,P. N.W.M. Breuls,J. J.J. Bucx,Jan H. Cornel,P. A. de Milliano,Peter H.J.M. Dunselman,B. J.B. Hamer,N. Holwerda,J. Hoogsteen,J. C.A. Hoorntje,Johannes A. Kragten,A. H. Liem,G. Linssen,H. R. Michels,A. R. Ramdat Misier,H. J. Schaafsma,P. Sijbring,R. J.T. Taverne,L. H.J. Van Kempen,R. Van Stralen,P. J. Van Veldhuisen,M. J. Veerhoek,C. J.P.J. Werter,J. C.L. Wesdorp,A. R. Willems,A. J.A.M. Withagen,P. A.G. Zwart,R. Bjornerheim,M. Dahle,Kenneth Dickstein,G. S. Froland,T. Gundersen,K. Hofsoy,T. L. Hole,T. Johansen,J. Mannsverk,P. Nesje,T. M. Omland,C. Sjödin,Peter K. Smith,H. A. Tjonndal,O. Vikesdal,K. Waage,Adamus,K. Jaworska,P. Kolodziej,Z. Kornacewicz-Jach,M. Krzemiñska-Pakula,J. W. Piotrowski,W. Piwowarska,A. Stogowski,J. Wodniecki,K. Wrabec,P. Ahlström,S. Ekdahl,L. O. Hemmingson,L. Holmberg,B. Lernfelt,H. Nilsson B Widgren,K. Ångman,P. Erne,P. Mohacsi,R. Polikar,H. Schläpfer,P. Batin,K. E. Berkin,T. S. Callaghan,J. Forfar,Michael P. Frenneaux,R A Greenbaum,M. Maltz,D. Murdoch,G. Reynolds,J. Stephens,Allan D. Struthers,J. Swan,G. Tildesley,A. Abbasi,P. Alagona,J. Alderman,M. Alipour,J. L. Anderson,Z. Ansari,M. Ashraf,B. T. Beanblossom,S. Bennett,D. Benvenuti,Martin R. Berk,R. Bhalla,Seth Bilazarian,K. F. Browne,C. MBuchter,R. Carlson,C. J. Carlson,K. Danisa,Ira Dauber,Marcus A. Dewood,G. Dennish,D. M. Denny,R. DiBianco,P. M. Diller,Mark E. Dunlap,K. Dowd,A. Edmiston,M. El Shahawy,Uri Elkayam,J. Farnham,P. Fenster,S. Friedman,T. Heywood,J. P. Galichia,Michael R. Geller,Jalal K. Ghali,Mihai Gheorghiade,T. Giles,R. Gillespe,G. Goldberg,M. C. Goldberg,D. A. Goldscher,G. P. Gooden,M. Goodman,L. Goodman,J. Gorwit,Shmuel Gottlieb,A. Gradman,D. Grech,T. Hack,J. H. Hall,M. T. Hattenhauer,M. B. Higginbotham,S. Hutchins,M. Imburgia,B. J. Iteld,B. Jackson,S. Jafri,W. Jauch,S. Jennison,B. H. Kahn,W. Kao,K. Kaplan,Ronald P. Karlsberg,Harold L. Kennedy,J. J. Kennedy,L. Kirkegaard,D. H. Kraus,K. LaBresh,L. Lalonde,M. F. Lesser,R. Levites,M. Levy,R. K. Lewis,Irving K. Loh,H. Madyoon,F. Maislos,Douglas L. Mann,G. L. Maurice,A. Nisar,W. Old,J. D. Pappas,K. Phadke,S. Promisloff,A. M. Rashkow,B. Reeves,J. H. Rosen,M. Rotman,T. Saleem,S. V. Savran,R. Shah,Y. Shalev,J. Shanes,M. O'Shaughnessy,B. Silverman,Richard M. Steingart,L. Swenson,K. Syed,U. Thadani,R. D. Thorsen,M. J. Tonkon,R. Touchon,G. Uhl,K. J. Vaska,S. G. Wagner,C. J. Weaver,Robert J. Weiss,W. J. Wickemeyer,H. J. Willens,J. R. Wilson,R. Wright,L. Yellen +350 more
TL;DR: Metoprolol controlled release/extended release (CR/XL) once daily in addition to standard therapy improved survival and the drug was well tolerated.
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The Effect of Carvedilol on Morbidity and Mortality in Patients with Chronic Heart Failure
Milton Packer,Michael R. Bristow,Jay N. Cohn,Wilson S. Colucci,Michael B. Fowler,Edward M. Gilbert,Neil H. Shusterman +6 more
TL;DR: Carvedilol reduces the risk or death as well as the risk of hospitalization for cardiovascular causes in patients with heart failure who are receiving treatment with digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor.
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The Effect of Carvedilol on Morbidity and Mortality in Patients With Chronic Heart Failure
Milton Packer,Michael R. Bristow,Jay N. Cohn,Wilson S. Colucci,Michael B. Fowler,Edward M. Gilbert,Neil H. Shusterman +6 more
TL;DR: In this paper, a double-blind, placebo-controlled, stratified program, in which patients were assigned to one of four treatment protocols on the basis of their exercise capacity, was presented.
ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 = Akut ve Kronik Kalp Yetersizligi Tani ve Tedavisine Yönelik 2012 ESC Kilavuzu
John J.V. McMurray,S. Adamopoulos,S.D. Anker,Angelo Auricchio,Michael Böhm,Kenneth Dickstein,Volkmar Falk,G. Filippatos,Candida Fonseca,Gomez-Sanchez,Trijntje Jaarsma,Lars Køber,G.Y. Lip,A.P. Maggioni,A. Parkhomenko,Burkert Pieske,Bogdan A. Popescu,K. Ronnevik,Frans H. Rutten,Juerg Schwitter,Petar M. Seferovic,Janina Stępińska,P.T. Trindade,A. A. Voors,F. Zannad,Andreas M. Zeiher +25 more
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ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008
John Camm,Veronica Dean,José Luis Zamorano,Perry M. Elliott,Ferenc Follath,Anders Hernborg,Luigi Tavazzi,Freek W.A. Verheugt +7 more
TL;DR: Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians and other healthcare providers in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means.
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