The cardiac sarcoplasmic/endoplasmic reticulum calcium ATPase: a potent target for cardiovascular diseases.
The cardiac isoform of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2a) is a calcium ion (Ca(2+)) pump powered by ATP hydrolysis. SERCA2a transfers Ca(2+) from the cytosol of the cardiomyocyte to the lumen of the sarcoplasmic reticulum during muscle relaxation. As such, this transporter has a key role in cardiomyocyte Ca(2+) regulation. In both experimental models and human heart failure, SERCA2a expression is significantly decreased, which leads to abnormal Ca(2+) handling and a deficient contractile state. Following a long line of investigations in isolated cardiac myocytes and small and large animal models, a clinical trial is underway that is restoring SERCA2a expression in patients with heart failure by use of adeno-associated virus type 1. Beyond its role in contractile abnormalities in heart failure, SERCA2a overexpression has beneficial effects in a host of other cardiovascular diseases. Here we describe the mechanism of Ca(2+) regulation by SERCA2a, examine the beneficial effects as well as the failures, risks and complexities associated with SERCA2a overexpression, and discuss the potential of SERCA2a as a target for the treatment of cardiovascular disease.
Kawase
Yoshiaki
Y
Mount Sinai School of Medicine, New York, NY 10029, USA.
Hajjar
Roger J
RJ
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000378:metabolism; D006332:Cardiomegaly / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D049109:Cell Proliferation; D003326:Coronary Circulation; D000229:Dependovirus / Q000235:genetics; D004734:Energy Metabolism; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D007527:Isoenzymes; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009200:Myocardial Contraction / Q000235:genetics; D009206:Myocardium / Q000201:enzymology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D007527:Isoenzymes; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban