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Transgenic Overexpression of the Ca2+-binding Protein S100A1 in the Heart Leads to Increasedin VivoMyocardial Contractile Performance

Patrick Most, Andrew Remppis, Sven T. Pleger, Eva Löffler, Philipp Ehlermann, Juliane Bernotat, Christiane Kleuss, Jörg Heierhorst, Patricia Ruiz, Henning Witt, Peter Karczewski, Lan Mao (+4 others)
2003 Journal of Biological Chemistry  

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S100A1, a Ca 2؉ -sensing protein of the EF-hand family, is most highly expressed in myocardial tissue, and cardiac S100A1 overexpression in vitro has been shown to enhance myocyte contractile properties. To study the physiological consequences of S100A1 in vivo, transgenic mice were developed with cardiac-restricted overexpression of S100A1. Characterization of two independent transgenic mouse lines with ϳ4-fold overexpression of S100A1 in the myocardium revealed a marked augmentation of in
more » ... basal cardiac function that remained elevated after ␤-adrenergic receptor stimulation. Contractile function and Ca 2؉ handling properties were increased in ventricular cardiomyocytes isolated from S100A1 transgenic mice. Enhanced cellular Ca 2؉ cycling by S100A1 was associated both with increased sarcoplasmic reticulum Ca 2؉ content and enhanced sarcoplasmic reticulum Ca 2؉ -induced Ca 2؉ release, and S100A1 was shown to associate with the cardiac ryanodine receptor. No alterations in ␤-adrenergic signal transduction or major cardiac Ca 2؉cycling proteins occurred, and there were no signs of hypertrophy with chronic cardiac S100A1 overexpression. Our findings suggest that S100A1 plays an important in vivo role in the regulation of cardiac function perhaps through interacting with the ryanodine receptor. Because S100A1 protein expression is downregulated in heart failure, increasing S100A1 expression in the heart may represent a novel means to augment contractility.
doi:10.1074/jbc.m301788200 pmid:12777394 fatcat:u7vjsqof3bb7vhrcnrl2p7ry74
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Patrick Most, Andrew Remppis, Sven T. Pleger, Eva Löffler, Philipp Ehlermann, Juliane Bernotat, Christiane Kleuss, Jörg Heierhorst, Patricia Ruiz, Henning Witt, Peter Karczewski, Lan Mao, Howard A. Rockman, Sandra J. Duncan, Hugo A. Katus, Walter J. Koch. "Transgenic Overexpression of the Ca2+-binding Protein S100A1 in the Heart Leads to Increasedin VivoMyocardial Contractile Performance." Journal of Biological Chemistry 278.36 (2003) 33809-33817