Tips from the American Journal of...(fibrillation which is characterized by u...),Health

Date:8/26/2009

fibrillation, which is characterized by uncoordinated activation of the atria in the heart, can cause heart failure, stroke, and thromboembolism. Inhibition of PI3K (p110α), a critical molecular signal for insulin, is associated with risk factors for atrial fibrillation, including aging, obesity, and diabetes.

To determine if PI3K (p110α) plays a role in atrial fibrillation, Pretorius et al examined a mouse model of dilated cardiomyopathy, where the heart becomes weak and large and cannot pump blood efficiently, with decreased levels of PI3K (p110α) expression. These mice developed atrial fibrillation and had depressed cardiac function, but increasing PI3K activity reduced the severity of these symptoms. Human patients with atrial fibrillation were found to have decreased levels of PI3K activity as well. Strategies to activate PI3K (p110α) may therefore prove to be new treatment options for atrial fibrillation and heart failure.

Pretorius et al "have developed a genetic mouse model of [atrial fibrillation] that is associated with heart failure and overt atrial remodelling, simulating the clinical situation. A reduction in PI3K(p110α) activity, a critical effector of insulin signaling, can help explain the link between risk factors such as aging, obesity and diabetes with [atrial fibrillation]. Strategies/agents that can activate PI3K(p110α) specifically in the heart may represent a therapeutic approach for heart failure and [atrial fibrillation]."

Pretorius L, Du X-J, Woodcock EA, Kiriazis H, Lin RCY, Marasco S, Medcalf RL, Ming Z, Head GA, Tan JW, Cemerlang N, Sadoshima J, Shioi T, Izumo S, Lukoshkova E, Dart AM, Jennings GL, McMullen JR: Reduced phosphoinositide 3-kinase (p110α) activation increases the susceptibility to atrial fibrillation. Am J Pathol 2009, 175: 998-1008

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Contact: Angela Colmone acolmone@asip.org 301-634-7953 American Journal of Pathology Source:Eurekalert

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