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The Contractile and Neurohormonal Roles of Phospholamban in Heart Failure

  • Chapter
Cardiac Remodeling and Failure

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 5))

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Abstract

Heart failure is a down-spiraling syndrome of neurohormonal imbalance and hemodynamic instability, in which impaired cardiac function has been linked to perturbations in subcellular calcium handling. Phospholamban (PLB) is a phosphoprotein that inhibits cardiac muscle relaxation by lowering the apparent affinity of the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2) for Ca2+. Major determinants of phospholamban s regulatory activity are the relative PLB/SERCA2 ratio and phospholamban’s phosphorylation status, both of which are altered in failing human hearts. PLB impairs myocardial calcium handling and observed perturbations of PLB levels and/or activity in human heart failure may contribute to depressed contractility. Therapeutic implications for PLB are intriguing, as PLB’s activity and levels are significantly influenced by specific neurohormonal systems.

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  1. Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati OH, 45267-0575, USA

    Rajesh Dash & Evangelia G. Kranias Ph.D.

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  1. Rajesh Dash
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  2. Evangelia G. Kranias Ph.D.
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Correspondence to Evangelia G. Kranias Ph.D. .

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  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Pawan K. Singal PhD, DSc (Professor), Ian M. C. Dixon PhD (Associate Professor), Lorrie A. Kirshenbaum PhD (Associate Professor) & Naranjan S. Dhalla PhD, MD (HON), DSc (HON) (Distinguished Professor and Director) (Professor),  (Associate Professor),  (Associate Professor) &  (Distinguished Professor and Director)

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Dash, R., Kranias, E.G. (2003). The Contractile and Neurohormonal Roles of Phospholamban in Heart Failure. In: Singal, P.K., Dixon, I.M.C., Kirshenbaum, L.A., Dhalla, N.S. (eds) Cardiac Remodeling and Failure. Progress in Experimental Cardiology, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9262-8_9

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  • DOI: https://doi.org/10.1007/978-1-4419-9262-8_9

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