title: Role of the dysfunctional ryanodine receptor - Na(+)-Ca(2+)exchanger axis in progression of cardiovascular diseases: What we can learn from pharmacological studies?
abstract: Abnormal Ca(2+)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 Ca(2+)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(+)-Ca(2+)exchanger in disturbances of Ca(2+)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(+)-Ca(2+)exchanger inhibition.
authors.affiliation: MTA-SZTE Research Group of Cardiovascular Pharmacology, Szeged, Hungary.
authors.forename: Károly
authors.initials: K
authors.lastname: Acsai
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Szeged, Faculty of Medicine, Szeged, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Ördög
authors.affiliation: MTA-SZTE Research Group of Cardiovascular Pharmacology, Szeged, Hungary; Department of Pharmacology and Pharmacotherapy, University of Szeged, Faculty of Medicine, Szeged, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Varró
authors.affiliation: Department of Physiology, University of Debrecen, Debrecen, Hungary; Department of Dentistry, University of Debrecen, Debrecen, Hungary. Electronic address: nanasi.peter@med.unideb.hu.
authors.forename: Péter P
authors.initials: PP
authors.lastname: Nánási
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D019831:Sodium-Calcium Exchanger
keywords: Ca(2+)homeostasis; Cardiac arrhythmia; Heart failure; Intracellular Ca(2+)concentration; Na(+)-Ca(2+)exchanger; Ryanodine receptor