Targeting Ca<SUP>2+</SUP>Handling Proteins for the Treatment of Heart Failure and Arrhythmias

Njegic, Alexandra, Wilson, Claire ORCID: 0000-0003-0456-1350 and Cartwright, Elizabeth J
(2020) Targeting Ca<SUP>2+</SUP>Handling Proteins for the Treatment of Heart Failure and Arrhythmias. FRONTIERS IN PHYSIOLOGY, 11. 1068-.

Access the full-text of this item by clicking on the Open Access link.


Diseases of the heart, such as heart failure and cardiac arrhythmias, are a growing socio-economic burden. Calcium (Ca<sup>2+</sup>) dysregulation is key hallmark of the failing myocardium and has long been touted as a potential therapeutic target in the treatment of a variety of cardiovascular diseases (CVD). In the heart, Ca<sup>2+</sup> is essential for maintaining normal cardiac function through the generation of the cardiac action potential and its involvement in excitation contraction coupling. As such, the proteins which regulate Ca<sup>2+</sup> cycling and signaling play a vital role in maintaining Ca<sup>2+</sup> homeostasis. Changes to the expression levels and function of Ca<sup>2+</sup>-channels, pumps and associated intracellular handling proteins contribute to altered Ca<sup>2+</sup> homeostasis in CVD. The remodeling of Ca<sup>2+</sup>-handling proteins therefore results in impaired Ca<sup>2+</sup> cycling, Ca<sup>2+</sup> leak from the sarcoplasmic reticulum and reduced Ca<sup>2+</sup> clearance, all of which contributes to increased intracellular Ca<sup>2+</sup>. Currently, approved treatments for targeting Ca<sup>2+</sup> handling dysfunction in CVD are focused on Ca<sup>2+</sup> channel blockers. However, whilst Ca<sup>2+</sup> channel blockers have been successful in the treatment of some arrhythmic disorders, they are not universally prescribed to heart failure patients owing to their ability to depress cardiac function. Despite the progress in CVD treatments, there remains a clear need for novel therapeutic approaches which are able to reverse pathophysiology associated with heart failure and arrhythmias. Given that heart failure and cardiac arrhythmias are closely associated with altered Ca<sup>2+</sup> homeostasis, this review will address the molecular changes to proteins associated with both Ca<sup>2+</sup>-handling and -signaling; their potential as novel therapeutic targets will be discussed in the context of pre-clinical and, where available, clinical data.

Item Type: Article
Uncontrolled Keywords: cardiovascular disease, heart failure, arrhythmia, calcium dysregulation, calcium
Depositing User: Symplectic Admin
Date Deposited: 27 Oct 2020 10:42
Last Modified: 12 Oct 2023 19:58
DOI: 10.3389/fphys.2020.01068
Open Access URL:
Related URLs: