Prevention of Myofilament Dysfunction by beta-Blocker Therapy in Postinfarct Remodeling
| Autor: | Lori A. Walker, Lucie Carrier, Daphne Merkus, Ger J.M. Stienen, Giulia Mearini, Amanda M. G. Versteilen, Judith Krysiak, Nicky M. Boontje, Wolfgang A. Linke, Jos M. J. Lamers, Vincent J. de Beer, Dirk J. Duncker, Ali El-Armouche, Jolanda van der Velden |
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| Přispěvatelé: | Physiology, ICaR - Heartfailure and pulmonary arterial hypertension, Cardiology, Biochemistry |
| Rok vydání: | 2009 |
| Předmět: |
Male
Myofilament medicine.medical_specialty Myosin Light Chains Time Factors Swine Adrenergic beta-Antagonists Myocardial Infarction Muscle Proteins Isometric exercise Contractility Ventricular Dysfunction Left Protein Phosphatase 1 Internal medicine medicine Animals Bisoprolol Myocyte Connectin Myocytes Cardiac Calcium Signaling Protein Phosphatase 2 Myocardial infarction Phosphorylation Protein kinase A Ventricular Remodeling business.industry Troponin I Recovery of Function medicine.disease Cyclic AMP-Dependent Protein Kinases Myocardial Contraction Actin Cytoskeleton Disease Models Animal Cardiology Female Carrier Proteins Cardiology and Cardiovascular Medicine Ligation business Cardiac Myosins Protein Kinases medicine.drug |
| Zdroj: | Duncker, D J, Boontje, N, Merkus, D, Versteilen, A M G, Krysiak, J, Mearini, G, El-Armouche, A, de Beer, V J, Lamers, J M J, Carrier, L, Walker, L A, Linke, W A, Stienen, G J M & van der Velden, J 2009, ' Prevention of myofilament dysfunction by beta-blocker therapy in postinfarct remodeling ', Circulation. Heart failure, vol. 2, no. 3, pp. 233-242 . https://doi.org/10.1161/CIRCHEARTFAILURE.108.806125 Circulation. Heart failure, 2(3), 233-242. Lippincott Williams and Wilkins Circulation-Heart Failure, 2(3), 233-242. Lippincott Williams & Wilkins |
| ISSN: | 1941-3289 |
| DOI: | 10.1161/circheartfailure.108.806125 |
| Popis: | Background— Myofilament contractility of individual cardiomyocytes is depressed in remote noninfarcted myocardium and contributes to global left ventricular pump dysfunction after myocardial infarction (MI). Here, we investigated whether β-blocker therapy could restore myofilament contractility. Methods and Results— In pigs with a MI induced by ligation of the left circumflex coronary artery, β-blocker therapy (bisoprolol, MI+β) was initiated on the first day after MI. Remote left ventricular subendocardial biopsies were taken 3 weeks after sham or MI surgery. Isometric force was measured in single permeabilized cardiomyocytes. Maximal force (F max ) was lower, whereas Ca 2+ sensitivity was higher in untreated MI compared with sham (both P 2+ sensitivity was abolished by treatment of cells with the β-adrenergic kinase, protein kinase A. β-blocker therapy partially reversed F max and Ca 2+ sensitivity to sham values and significantly reduced passive force. Despite the lower myofilament Ca 2+ sensitivity in MI+β compared with untreated myocardium, the protein kinase A induced reduction in Ca 2+ sensitivity was largest in cardiomyocytes from myocardium treated with β-blockers. Phosphorylation of β-adrenergic target proteins (myosin binding protein C and troponin I) did not differ among groups, whereas myosin light chain 2 phosphorylation was reduced in MI, which coincided with increased expression of protein phosphatase 1. β-blockade fully restored the latter alterations and significantly reduced expression of protein phosphatase 2a. Conclusions— β-blockade reversed myofilament dysfunction and enhanced myofilament responsiveness to protein kinase A in remote myocardium after MI. These effects likely contribute to the beneficial effects of β-blockade on global left ventricular function after MI. |
| Databáze: | OpenAIRE |
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