Cardiac calcium handling on trial: editorial
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 i...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
January 2, 2014
|
| In: |
Circulation research
Year: 2014, Volume: 114, Issue: 1, Pages: 12-14 |
| ISSN: | 1524-4571 |
| DOI: | 10.1161/CIRCRESAHA.113.302748 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1161/CIRCRESAHA.113.302748 Verlag, Volltext: http://circres.ahajournals.org/content/114/1/12 
|
| Author Notes: | Sven T. Pleger, Philip Raake, Hugo A. Katus, Patrick Most |
| Summary: | 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 . … |
|---|---|
| Item Description: | Gesehen am 23.12.2016 |
| Physical Description: | Online Resource |
| ISSN: | 1524-4571 |
| DOI: | 10.1161/CIRCRESAHA.113.302748 |