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(Circulation Research. 2005;96:708.)
© 2005 American Heart Association, Inc.

Editorials

Targeting Protein Phosphatase 1 in Heart Failure

Hunter C. Champion

From the Divisions of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md.

Correspondence to Hunter C. Champion, MD, PhD, Division of Cardiology, Johns Hopkins Medical Institutions, 720 Rutland Avenue, Ross 850, Baltimore, MD 21205. E-mail hcc@jhmi.edu

See related article, pages 756–766

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Over the past three decades the treatment of heart failure has shifted from a palliative care approach to a more successful focus on neurohormonal modulation through drugs that inhibit ß-adrenergic, angiotensin, and aldosterone signaling. Despite these relatively recent advances, the clinical syndrome of heart failure remains progressive in nature. This observation begs the question as to a unifying aberrancy in cardiomyocyte phenotype that occurs in heart failure. More recently great attention has been paid to the alterations in calcium handling and has typically been associated with calcium-transients that are of a lower amplitude and slower decline than normal cardiomyocytes.^1–4 This slower decline has been attributed to a decrease in the Ca²⁺ uptake into the sarcoplasmic reticulum (SR); and particularly with the relative role of phospholamban (PLB) and the SR Ca²⁺-ATPase (SERCA).^4,5 Whereas previous work has successfully targeted PLB and SERCA in the investigational treatment of heart failure in mouse, rat, and human myocytes, more recent work has focused on the potential modulators of this system to elucidate the pathophysiologic changes that result in aberrant calcium handling.^2–6

In this issue, Pathak and del Monte et al show that targeted inhibition of protein phosphatase 1 (PP1) by increased activity of its inhibitor, inhibitor-1 in the heart, results in enhanced contractility and is protective against the development of cardiac hypertrophy and heart failure stimulated by hemodynamic load.⁷ In failing hearts, the downregulation of adrenergic receptor and cAMP-dependent protein kinase signaling leads to the inactivation of inhibitor-1 which, in turn, results in increased . . . [Full Text of this Article]

Related Article:

Enhancement of Cardiac Function and Suppression of Heart Failure Progression By Inhibition of Protein Phosphatase 1

Anand Pathak, Federica del Monte, Wen Zhao, Jo-El Schultz, John N. Lorenz, Ilona Bodi, Doug Weiser, Harvey Hahn, Andrew N. Carr, Faisal Syed, Nirmala Mavila, Leena Jha, Jiang Qian, Yehia Marreez, Guoli Chen, Dennis W. McGraw, E. Kevin Heist, J. Luis Guerrero, Anna A. DePaoli-Roach, Roger J. Hajjar, and Evangelia G. Kranias
Circ. Res. 2005 96: 756-766. [Abstract] [Full Text] [PDF]

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