Study Seeks Novel Treatment for Heart Rhythm Disorder

In search of the first effective means to treat and prevent this debilitating disease, Ozcan also will work to identify novel molecular targets.

Her research is funded with a $766,000, five-year grant from the National Heart, Lung and Blood Institute.

“There is currently no effective therapy for prevention and optimal treatment of atrial fibrillation, since the molecular mechanisms and the mechanistic therapeutic targets are not known,” Ozcan explains.

“My study develops an original approach for the prevention and treatment of atrial fibrillation by targeting molecular mechanisms of the disease process,” she says.

“The findings provide a framework for novel therapies and will have enormous impact on millions of patients around the world.”

Ozcan’s team is focusing on the role of mitochondria — cellular organelles that produce energy for normal cellular function and survival.

Ozcan believes that mitochondrial dysfunction plays a critical role in atrial fibrillation.

Dysfunction causes metabolic and oxidative stress linked to the depletion of adenosine triphosphate (ATP), an energy-storing molecule. It also disrupts ionic currents and membrane potential, and increases the generation of reactive oxygen species.

Ozcan’s prior research demonstrated that impaired mitochondrial energetics and oxidative stress induce arrhythmias or irregular heartbeats as well as the loss of myocytes — cells found in muscle tissue, including the heart.

Ozcan will now evaluate molecular and cellular changes associated with the onset of the disease, focusing on two protective pathways: mitochondrial ATP-sensitive potassium channel and uncoupling proteins.

Activation of these pathways protects cardiomyocytes by reducing oxidative stress and preserving mitochondrial bioenergetics.

The researchers will determine whether these pathways are disrupted in atrial fibrillation and if therapy can reverse disruptive changes.

They will use two novel, distinct animal models of the disorder, one with rapid atrial pacing and another with disruption of the liver kinase B1 protein.

Ozcan’s grant is a K08 Mentored Clinical Scientist Research Career Development Award. Through these awards, the National Institutes of Health supports scientists whose work contributes significantly to the nation’s health-related research needs.

Atrial fibrillation is a major public health problem afflicting millions of Americans — 1 percent of the U.S. population. It is associated with higher risks of a host of serious consequences, including:

• stroke
• heart failure
• blockage or clotting events
• dementia
• impaired quality of life
• death

A specialist in cardiac electrophysiology, Ozcan also is a practicing physician in the Buffalo area. She focuses on treating patients with complex arrhythmias, in part with device therapies, such as pacemakers.