Role of the dysfunctional ryanodine receptor - Na+-Ca2+ exchanger axis in progression of cardiovascular diseases: What we can learn from pharmacological studies?

Abnormal Ca2+ homeostasis is often associated with chronic cardiovascular diseases, such as hypertension, heart failure or cardiac arrhythmias, and typically contributes to the basic ethiology of the disease. Pharmacological targeting of cardiac Ca2+ handling has great therapeutic potential offering invaluable options for the prevention, slowing down the progression or suppression of the harmful outcomes like life threatening cardiac arrhythmias. In this review we outline the existing knowledge on the involvement of malfunction of the ryanodine receptor and the Na+-Ca2+ exchanger in disturbances of Ca2+ homeostasis and discuss important proof of concept pharmacological studies targeting these mechanisms in context of hypertension, heart failure, atrial fibrillation and ventricular arrhythmias. We emphasize the promising results of preclinical studies underpinning the potential benefits of the therapeutic strategies based on ryanodine receptor or Na+-Ca2+ exchanger inhibition. (C) 2016 Elsevier B.V. All rights reserved.