Cardiac calcium handling on trial

• Verfasst von: Pleger, Sven Torsten [VerfasserIn]
• Verfasst von: Raake, Philip [VerfasserIn]
• Verfasst von: Katus, Hugo [VerfasserIn]
• Verfasst von: Most, Patrick [VerfasserIn]
• Titel: Cardiac calcium handling on trial
• Titelzusatz: editorial
• Verf.angabe: Sven T. Pleger, Philip Raake, Hugo A. Katus, Patrick Most
• Umfang: 3 S.
• Fussnoten: Gesehen am 23.12.2016
• Titel Quelle: Enthalten in: Circulation research
• Jahr Quelle: 2014
• Band/Heft Quelle: 114(2014), 1, S. 12-14
• ISSN Quelle: 1524-4571
• DOI: doi:10.1161/CIRCRESAHA.113.302748
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1551262088

Abstract

Targeting abnormal calcium (Ca)2+ handling in ventricular cardiomyocytes emerged as a new paradigm for human heart failure (HF) therapy.1 Cardiomyocytes come with an extensive Ca2+ signaling toolkit consisting of various Ca2+ transporters, Ca2+ channels, Ca2+ buffer, and sensor proteins. Organized into self-contained signaling modules in which Ca2+ signaling functions within highly localized environments, the cardiac Ca2+ signalosome delivers dynamic signals with different spatial and temporal properties that relay compartmentalized Ca2+ oscillations into specific cellular functions.2 As a result, Ca2+ governs not only the cardiomyocyte contractile cycle, but also concurrently control transcription and muscle growth, electric excitability, cell survival, and energy metabolism.3 Article, see p 101. Key components of the cardiac Ca2+ signalosome remodel as a molecular hallmark in HF: loss of sarco(endo)plasmic reticulum ATPase 2a (SERCA2a) expression surfaced as 1 critical abnormality in experimental HF and human failing myocardium. The defect alone is sufficient to disable various Ca2+-dependent homeostatic mechanisms that drive further deterioration of cardiac function and structure after a primary insult, such as myocardial infarction.1 Translational studies, particularly in human-relevant large animal models, have successfully used recombinant adeno-associated viral (rAAV) vectors for cardiac- targeted delivery of therapeutically formulated synthetic SERCA2a DNA that resulted in safe and long-term restoration of cardiac function and reversal of structural, electric, and metabolic remodeling in experimental HF.4 Hence, targeting defective components of the cardiomyocyte Ca2+ signalosome in HF might bear therapeutic benefits beyond sole improvement of cardiac contractile performance (Figure). Figure. Calcium (Ca)2+ regulation of cardiomyocyte function is not limited to contractile performance but extends to control over nuclear transcription, electric activity, cell survival, and energy metabolism . …