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Istaroxime stimulates SERCA2a and accelerates calcium cycling in heart failure by relieving phospholamban inhibition
Author(s) -
Ferrandi Mara,
Barassi Paolo,
TadiniBuoninsegni Francesco,
Bartolommei Gianluca,
Molinari Isabella,
Tripodi Maria Grazia,
Reina Cristina,
Moncelli Maria Rosa,
Bianchi Giuseppe,
Ferrari Patrizia
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12278
Subject(s) - phospholamban , heart failure , contractility , inotrope , calcium , serca , chemistry , pharmacology , endocrinology , medicine , atpase , biochemistry , enzyme
Calcium handling is known to be deranged in heart failure. Interventions aimed at improving cell Ca(2) (+) cycling may represent a promising approach to heart failure therapy. Istaroxime is a new luso-inotropic compound that stimulates cardiac contractility and relaxation in healthy and failing animal models and in patients with acute heart failure (AHF) syndrome. Istaroxime is a Na-K ATPase inhibitor with the unique property of increasing sarcoplasmic reticulum (SR) SERCA2a activity as shown in heart microsomes from humans and guinea pigs. The present study addressed the molecular mechanism by which istaroxime increases SERCA2a activity.