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1 Department of Medicine, University of California, San Diego, San Diego, CA, USA
2 Department of Pharmacology, University of California, San Diego, San Diego, CA, USA
* To whom correspondence should be addressed. E-mail: wdillmann{at}ucsd.edu.
In many types of heart failure cardiac myocyte calcium handling is abnormal due to downregulation of key calcium-handling proteins like the Ca2+ ATPase of the sarcoplasmic reticulum (SERCA2a) and ryanodine receptor (RyR2). The alteration in SERCA2a and RyR2 expression results in altered cytosolic calcium transients leading to abnormal contraction. Sorcin is an EF-hand protein that confers the property of caffeine-activated intracellular Ca2+ release in nonmuscle cells by interacting with the RyR2. To determine if sorcin could improve the contractile function of the heart, we overexpressed sorcin in the heart of either normal or diabetic mice and in adult rat cardiomyocytes using an adenoviral gene transfer approach. Sorcin overexpression was associated with an increase in cardiac contractility of the normal heart and dramatically rescued the abnormal contractile function of the diabetic heart. These effects could be attributed to an improvement of the calcium transients found in the cardiomyocyte after sorcin overexpression. Viral vector mediated delivery of sorcin to cardiac myocytes is beneficial resulting in improved contractile function in diabetic cardiomyopathy.
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