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(Circulation. 2008;117:1769.)
© 2008 American Heart Association, Inc.

Clinical Summaries

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Conditional FKBP12.6 Overexpression in Mouse Cardiac Myocytes Prevents Triggered Ventricular Tachycardia Through Specific Alterations in Excitation-Contraction Coupling

 
Ventricular arrhythmias are a frequent fatal outcome during chronic heart failure. As is the case in catecholaminergic ventricular tachycardia, they seem to result from a leak out of the sarcoplasmic reticulum (SR) during diastole, itself favored by stress. The ryanodine receptor (RyR2) is the SR channel through which calcium normally comes out of the SR during systole to trigger contraction and leaks out of the SR during diastole. It has been suggested that RyR2 leakage may be favored by the unbinding from RyR2 of the small regulatory protein FKBP12.6, also known as calstabin 2. In the present study, we show in a mouse model that increasing the expression level of FKBP12.6 in cardiac myocytes results in increased FKBP12.6 binding to RyR2, even when the latter is hyperphosphorylated, a feature associated with a decreased rate of ventricular tachycardia triggered by burst pacing in stress conditions, and a reduced SR calcium leak in isolated myocytes. Our results firmly support the hypothesis that the FKBP12.6-RyR2 complex is an important candidate target for pharmacological prevention of ventricular tachycardia. Other studies are now needed to determine precisely how FKBP12.6 binding to a hyperphosphorylated RyR2 exerts this beneficial effect and to identify new molecules that may favor this binding. See p 1778.

	Impact of Ethnicity and Gender Differences on Angiographic Coronary Artery Disease Prevalence and In-Hospital Mortality in the American College of Cardiology–National Cardiovascular Data Registry

 
Dramatic population shifts have made the United States ever more ethnically diverse. Its healthcare centers reflect this ethnic "melting pot," yet our understanding of diverse healthcare needs and differences in disease prevalence and outcomes between male and female ethnic subsets remains poor. The . . . [Full Text of this Article]

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